diff --git a/Include/cpython/pylifecycle.h b/Include/cpython/pylifecycle.h
index d425a233f71000..e46dfe59ec4630 100644
--- a/Include/cpython/pylifecycle.h
+++ b/Include/cpython/pylifecycle.h
@@ -63,6 +63,15 @@ typedef struct {
         .gil = PyInterpreterConfig_OWN_GIL, \
     }
 
+// gh-117649: The free-threaded build does not currently support single-phase
+// init extensions in subinterpreters. For now, we ensure that
+// `check_multi_interp_extensions` is always `1`, even in the legacy config.
+#ifdef Py_GIL_DISABLED
+#  define _PyInterpreterConfig_LEGACY_CHECK_MULTI_INTERP_EXTENSIONS 1
+#else
+#  define _PyInterpreterConfig_LEGACY_CHECK_MULTI_INTERP_EXTENSIONS 0
+#endif
+
 #define _PyInterpreterConfig_LEGACY_INIT \
     { \
         .use_main_obmalloc = 1, \
@@ -70,7 +79,7 @@ typedef struct {
         .allow_exec = 1, \
         .allow_threads = 1, \
         .allow_daemon_threads = 1, \
-        .check_multi_interp_extensions = 0, \
+        .check_multi_interp_extensions = _PyInterpreterConfig_LEGACY_CHECK_MULTI_INTERP_EXTENSIONS, \
         .gil = PyInterpreterConfig_SHARED_GIL, \
     }
 
diff --git a/Lib/test/support/__init__.py b/Lib/test/support/__init__.py
index 4bf2d7b5142da9..be3f93ab2e5fd1 100644
--- a/Lib/test/support/__init__.py
+++ b/Lib/test/support/__init__.py
@@ -842,6 +842,12 @@ def requires_gil_enabled(msg="needs the GIL enabled"):
     """Decorator for skipping tests on the free-threaded build."""
     return unittest.skipIf(Py_GIL_DISABLED, msg)
 
+def expected_failure_if_gil_disabled():
+    """Expect test failure if the GIL is disabled."""
+    if Py_GIL_DISABLED:
+        return unittest.expectedFailure
+    return lambda test_case: test_case
+
 if Py_GIL_DISABLED:
     _header = 'PHBBInP'
 else:
diff --git a/Lib/test/test_capi/test_misc.py b/Lib/test/test_capi/test_misc.py
index 35d6a209122a99..8cdecaf3626401 100644
--- a/Lib/test/test_capi/test_misc.py
+++ b/Lib/test/test_capi/test_misc.py
@@ -26,6 +26,8 @@
 from test.support import threading_helper
 from test.support import warnings_helper
 from test.support import requires_limited_api
+from test.support import requires_gil_enabled, expected_failure_if_gil_disabled
+from test.support import Py_GIL_DISABLED
 from test.support.script_helper import assert_python_failure, assert_python_ok, run_python_until_end
 try:
     import _posixsubprocess
@@ -2023,15 +2025,30 @@ def test_configured_settings(self):
         kwlist[-2] = 'check_multi_interp_extensions'
         kwlist[-1] = 'own_gil'
 
-        # expected to work
-        for config, expected in {
+        expected_to_work = {
             (True, True, True, True, True, True, True):
                 (ALL_FLAGS, True),
             (True, False, False, False, False, False, False):
                 (OBMALLOC, False),
             (False, False, False, True, False, True, False):
                 (THREADS | EXTENSIONS, False),
-        }.items():
+        }
+
+        expected_to_fail = {
+            (False, False, False, False, False, False, False),
+        }
+
+        # gh-117649: The free-threaded build does not currently allow
+        # setting check_multi_interp_extensions to False.
+        if Py_GIL_DISABLED:
+            for config in list(expected_to_work.keys()):
+                kwargs = dict(zip(kwlist, config))
+                if not kwargs['check_multi_interp_extensions']:
+                    del expected_to_work[config]
+                    expected_to_fail.add(config)
+
+        # expected to work
+        for config, expected in expected_to_work.items():
             kwargs = dict(zip(kwlist, config))
             exp_flags, exp_gil = expected
             expected = {
@@ -2055,9 +2072,7 @@ def test_configured_settings(self):
                 self.assertEqual(settings, expected)
 
         # expected to fail
-        for config in [
-            (False, False, False, False, False, False, False),
-        ]:
+        for config in expected_to_fail:
             kwargs = dict(zip(kwlist, config))
             with self.subTest(config):
                 script = textwrap.dedent(f'''
@@ -2070,6 +2085,9 @@ def test_configured_settings(self):
 
     @unittest.skipIf(_testsinglephase is None, "test requires _testsinglephase module")
     @unittest.skipUnless(hasattr(os, "pipe"), "requires os.pipe()")
+    # gh-117649: The free-threaded build does not currently allow overriding
+    # the check_multi_interp_extensions setting.
+    @expected_failure_if_gil_disabled()
     def test_overridden_setting_extensions_subinterp_check(self):
         """
         PyInterpreterConfig.check_multi_interp_extensions can be overridden
@@ -2165,6 +2183,9 @@ def test_mutate_exception(self):
         self.assertFalse(hasattr(binascii.Error, "foobar"))
 
     @unittest.skipIf(_testmultiphase is None, "test requires _testmultiphase module")
+    # gh-117649: The free-threaded build does not currently support sharing
+    # extension module state between interpreters.
+    @expected_failure_if_gil_disabled()
     def test_module_state_shared_in_global(self):
         """
         bpo-44050: Extension module state should be shared between interpreters
@@ -2223,7 +2244,7 @@ class InterpreterConfigTests(unittest.TestCase):
             allow_exec=True,
             allow_threads=True,
             allow_daemon_threads=True,
-            check_multi_interp_extensions=False,
+            check_multi_interp_extensions=bool(Py_GIL_DISABLED),
             gil='shared',
         ),
         'empty': types.SimpleNamespace(
@@ -2386,6 +2407,8 @@ def test_interp_init(self):
                 check_multi_interp_extensions=False
             ),
         ]
+        if Py_GIL_DISABLED:
+            invalid.append(dict(check_multi_interp_extensions=False))
         def match(config, override_cases):
             ns = vars(config)
             for overrides in override_cases:
@@ -2427,6 +2450,8 @@ def new_interp(config):
         with self.subTest('main'):
             expected = _interpreters.new_config('legacy')
             expected.gil = 'own'
+            if Py_GIL_DISABLED:
+                expected.check_multi_interp_extensions = False
             interpid, *_ = _interpreters.get_main()
             config = _interpreters.get_config(interpid)
             self.assert_ns_equal(config, expected)
@@ -2448,6 +2473,7 @@ def new_interp(config):
                 'empty',
                 use_main_obmalloc=True,
                 gil='shared',
+                check_multi_interp_extensions=bool(Py_GIL_DISABLED),
             )
             with new_interp(orig) as interpid:
                 config = _interpreters.get_config(interpid)
diff --git a/Lib/test/test_import/__init__.py b/Lib/test/test_import/__init__.py
index 6678548a0ffaca..4726619b08edc4 100644
--- a/Lib/test/test_import/__init__.py
+++ b/Lib/test/test_import/__init__.py
@@ -30,7 +30,8 @@
 from test.support import os_helper
 from test.support import (
     STDLIB_DIR, swap_attr, swap_item, cpython_only, is_apple_mobile, is_emscripten,
-    is_wasi, run_in_subinterp, run_in_subinterp_with_config, Py_TRACE_REFS)
+    is_wasi, run_in_subinterp, run_in_subinterp_with_config, Py_TRACE_REFS,
+    requires_gil_enabled, Py_GIL_DISABLED)
 from test.support.import_helper import (
     forget, make_legacy_pyc, unlink, unload, ready_to_import,
     DirsOnSysPath, CleanImport, import_module)
@@ -158,6 +159,9 @@ def meth(self, _meth=meth):
             finally:
                 restore__testsinglephase()
     meth = cpython_only(meth)
+    # gh-117649: free-threaded build does not currently support single-phase
+    # init modules in subinterpreters.
+    meth = requires_gil_enabled(meth)
     return unittest.skipIf(_testsinglephase is None,
                            'test requires _testsinglephase module')(meth)
 
@@ -1876,8 +1880,9 @@ def test_builtin_compat(self):
         # since they still don't implement multi-phase init.
         module = '_imp'
         require_builtin(module)
-        with self.subTest(f'{module}: not strict'):
-            self.check_compatible_here(module, strict=False)
+        if not Py_GIL_DISABLED:
+            with self.subTest(f'{module}: not strict'):
+                self.check_compatible_here(module, strict=False)
         with self.subTest(f'{module}: strict, not fresh'):
             self.check_compatible_here(module, strict=True)
 
@@ -1888,8 +1893,9 @@ def test_frozen_compat(self):
         require_frozen(module, skip=True)
         if __import__(module).__spec__.origin != 'frozen':
             raise unittest.SkipTest(f'{module} is unexpectedly not frozen')
-        with self.subTest(f'{module}: not strict'):
-            self.check_compatible_here(module, strict=False)
+        if not Py_GIL_DISABLED:
+            with self.subTest(f'{module}: not strict'):
+                self.check_compatible_here(module, strict=False)
         with self.subTest(f'{module}: strict, not fresh'):
             self.check_compatible_here(module, strict=True)
 
@@ -1908,8 +1914,9 @@ def test_single_init_extension_compat(self):
     def test_multi_init_extension_compat(self):
         module = '_testmultiphase'
         require_extension(module)
-        with self.subTest(f'{module}: not strict'):
-            self.check_compatible_here(module, strict=False)
+        if not Py_GIL_DISABLED:
+            with self.subTest(f'{module}: not strict'):
+                self.check_compatible_here(module, strict=False)
         with self.subTest(f'{module}: strict, not fresh'):
             self.check_compatible_here(module, strict=True)
         with self.subTest(f'{module}: strict, fresh'):
@@ -1930,8 +1937,9 @@ def test_multi_init_extension_non_isolated_compat(self):
             self.check_incompatible_here(modname, filename, isolated=True)
         with self.subTest(f'{modname}: not isolated'):
             self.check_incompatible_here(modname, filename, isolated=False)
-        with self.subTest(f'{modname}: not strict'):
-            self.check_compatible_here(modname, filename, strict=False)
+        if not Py_GIL_DISABLED:
+            with self.subTest(f'{modname}: not strict'):
+                self.check_compatible_here(modname, filename, strict=False)
 
     @unittest.skipIf(_testmultiphase is None, "test requires _testmultiphase module")
     def test_multi_init_extension_per_interpreter_gil_compat(self):
@@ -1949,16 +1957,18 @@ def test_multi_init_extension_per_interpreter_gil_compat(self):
         with self.subTest(f'{modname}: not isolated, strict'):
             self.check_compatible_here(modname, filename,
                                        strict=True, isolated=False)
-        with self.subTest(f'{modname}: not isolated, not strict'):
-            self.check_compatible_here(modname, filename,
-                                       strict=False, isolated=False)
+        if not Py_GIL_DISABLED:
+            with self.subTest(f'{modname}: not isolated, not strict'):
+                self.check_compatible_here(modname, filename,
+                                           strict=False, isolated=False)
 
     @unittest.skipIf(_testinternalcapi is None, "requires _testinternalcapi")
     def test_python_compat(self):
         module = 'threading'
         require_pure_python(module)
-        with self.subTest(f'{module}: not strict'):
-            self.check_compatible_here(module, strict=False)
+        if not Py_GIL_DISABLED:
+            with self.subTest(f'{module}: not strict'):
+                self.check_compatible_here(module, strict=False)
         with self.subTest(f'{module}: strict, not fresh'):
             self.check_compatible_here(module, strict=True)
         with self.subTest(f'{module}: strict, fresh'):
diff --git a/Lib/test/test_importlib/test_util.py b/Lib/test/test_importlib/test_util.py
index 115cb7a56c98f7..f0583c5fd0196f 100644
--- a/Lib/test/test_importlib/test_util.py
+++ b/Lib/test/test_importlib/test_util.py
@@ -682,6 +682,9 @@ def ensure_destroyed():
                 raise ImportError(excsnap.msg)
 
     @unittest.skipIf(_testsinglephase is None, "test requires _testsinglephase module")
+    # gh-117649: single-phase init modules are not currently supported in
+    # subinterpreters in the free-threaded build
+    @support.expected_failure_if_gil_disabled()
     def test_single_phase_init_module(self):
         script = textwrap.dedent('''
             from importlib.util import _incompatible_extension_module_restrictions
@@ -706,6 +709,7 @@ def test_single_phase_init_module(self):
                 self.run_with_own_gil(script)
 
     @unittest.skipIf(_testmultiphase is None, "test requires _testmultiphase module")
+    @support.requires_gil_enabled("gh-117649: not supported in free-threaded build")
     def test_incomplete_multi_phase_init_module(self):
         # Apple extensions must be distributed as frameworks. This requires
         # a specialist loader.
diff --git a/Lib/test/test_interpreters/test_api.py b/Lib/test/test_interpreters/test_api.py
index abf66a7cde796c..769bb7bfdb5a32 100644
--- a/Lib/test/test_interpreters/test_api.py
+++ b/Lib/test/test_interpreters/test_api.py
@@ -10,6 +10,7 @@
 from test.support import import_helper
 # Raise SkipTest if subinterpreters not supported.
 _interpreters = import_helper.import_module('_xxsubinterpreters')
+from test.support import Py_GIL_DISABLED
 from test.support import interpreters
 from test.support.interpreters import (
     InterpreterError, InterpreterNotFoundError, ExecutionFailed,
@@ -1162,7 +1163,7 @@ def test_new_config(self):
                 allow_exec=True,
                 allow_threads=True,
                 allow_daemon_threads=True,
-                check_multi_interp_extensions=False,
+                check_multi_interp_extensions=bool(Py_GIL_DISABLED),
                 gil='shared',
             ),
             'empty': types.SimpleNamespace(
@@ -1361,6 +1362,7 @@ def test_create(self):
         with self.subTest('custom'):
             orig = _interpreters.new_config('empty')
             orig.use_main_obmalloc = True
+            orig.check_multi_interp_extensions = bool(Py_GIL_DISABLED)
             orig.gil = 'shared'
             interpid = _interpreters.create(orig)
             config = _interpreters.get_config(interpid)
@@ -1410,13 +1412,8 @@ def test_get_config(self):
         with self.subTest('main'):
             expected = _interpreters.new_config('legacy')
             expected.gil = 'own'
-            interpid, *_ = _interpreters.get_main()
-            config = _interpreters.get_config(interpid)
-            self.assert_ns_equal(config, expected)
-
-        with self.subTest('main'):
-            expected = _interpreters.new_config('legacy')
-            expected.gil = 'own'
+            if Py_GIL_DISABLED:
+                expected.check_multi_interp_extensions = False
             interpid, *_ = _interpreters.get_main()
             config = _interpreters.get_config(interpid)
             self.assert_ns_equal(config, expected)
diff --git a/Lib/test/test_threading.py b/Lib/test/test_threading.py
index a7701fa285aee2..a712ed10f022d6 100644
--- a/Lib/test/test_threading.py
+++ b/Lib/test/test_threading.py
@@ -1527,6 +1527,7 @@ def func():
             {before_start}
             t.start()
             """)
+        check_multi_interp_extensions = bool(support.Py_GIL_DISABLED)
         script = textwrap.dedent(f"""
             import test.support
             test.support.run_in_subinterp_with_config(
@@ -1536,7 +1537,7 @@ def func():
                 allow_exec=True,
                 allow_threads={allowed},
                 allow_daemon_threads={daemon_allowed},
-                check_multi_interp_extensions=False,
+                check_multi_interp_extensions={check_multi_interp_extensions},
                 own_gil=False,
             )
             """)
diff --git a/Python/import.c b/Python/import.c
index 6544a84d895d4a..b040c7d5c0f7f5 100644
--- a/Python/import.c
+++ b/Python/import.c
@@ -3696,9 +3696,16 @@ _imp__override_multi_interp_extensions_check_impl(PyObject *module,
                         "cannot be used in the main interpreter");
         return NULL;
     }
+#ifdef Py_GIL_DISABLED
+    PyErr_SetString(PyExc_RuntimeError,
+                    "_imp._override_multi_interp_extensions_check() "
+                    "cannot be used in the free-threaded build");
+    return NULL;
+#else
     int oldvalue = OVERRIDE_MULTI_INTERP_EXTENSIONS_CHECK(interp);
     OVERRIDE_MULTI_INTERP_EXTENSIONS_CHECK(interp) = override;
     return PyLong_FromLong(oldvalue);
+#endif
 }
 
 #ifdef HAVE_DYNAMIC_LOADING
diff --git a/Python/pylifecycle.c b/Python/pylifecycle.c
index 4e83b1671a5029..efb25878312d85 100644
--- a/Python/pylifecycle.c
+++ b/Python/pylifecycle.c
@@ -559,6 +559,15 @@ init_interp_settings(PyInterpreterState *interp,
         return _PyStatus_ERR("per-interpreter obmalloc does not support "
                              "single-phase init extension modules");
     }
+#ifdef Py_GIL_DISABLED
+    if (!_Py_IsMainInterpreter(interp) &&
+        !config->check_multi_interp_extensions)
+    {
+        return _PyStatus_ERR("The free-threaded build does not support "
+                             "single-phase init extension modules in "
+                             "subinterpreters");
+    }
+#endif
 
     if (config->allow_fork) {
         interp->feature_flags |= Py_RTFLAGS_FORK;
@@ -647,8 +656,10 @@ pycore_create_interpreter(_PyRuntimeState *runtime,
     }
 
     PyInterpreterConfig config = _PyInterpreterConfig_LEGACY_INIT;
-    // The main interpreter always has its own GIL.
+    // The main interpreter always has its own GIL and supports single-phase
+    // init extensions.
     config.gil = PyInterpreterConfig_OWN_GIL;
+    config.check_multi_interp_extensions = 0;
     status = init_interp_settings(interp, &config);
     if (_PyStatus_EXCEPTION(status)) {
         return status;