diff --git a/chrome/browser/ash/file_manager/guest_os_file_tasks.cc b/chrome/browser/ash/file_manager/guest_os_file_tasks.cc
index fefdca4ca19bf5..7db251a1204773 100644
--- a/chrome/browser/ash/file_manager/guest_os_file_tasks.cc
+++ b/chrome/browser/ash/file_manager/guest_os_file_tasks.cc
@@ -112,8 +112,8 @@ bool HasSupportedExtension(const std::set<std::string>& supported_extensions,
   const auto& extension = entry.path.Extension();
   if (extension.size() <= 1 || extension[0] != '.')
     return false;
-  // Strip the leading period.
-  return supported_extensions.find({extension.begin() + 1, extension.end()}) !=
+  // Strip the leading period, convert to lower case for insensitive match.
+  return supported_extensions.find(base::ToLowerASCII(extension.substr(1))) !=
          supported_extensions.end();
 }
 
diff --git a/chrome/browser/ash/file_manager/guest_os_file_tasks_unittest.cc b/chrome/browser/ash/file_manager/guest_os_file_tasks_unittest.cc
index 3128d79f49b9c6..1ed49589229a41 100644
--- a/chrome/browser/ash/file_manager/guest_os_file_tasks_unittest.cc
+++ b/chrome/browser/ash/file_manager/guest_os_file_tasks_unittest.cc
@@ -175,6 +175,16 @@ TEST_F(GuestOsFileTasksTest, PluginVm_AppRegistered) {
   EXPECT_THAT(app_vm_types_, testing::ElementsAre(PLUGIN_VM));
 }
 
+TEST_F(GuestOsFileTasksTest, PluginVm_IgnoreCase) {
+  AddApp("app1", "name1", {}, {"Txt"}, PLUGIN_VM);
+  AddEntry("entry.txT", "test/mime1");
+  FindGuestOsApps(&profile_, entries_, urls_, &app_ids_, &app_names_,
+                  &app_vm_types_);
+  EXPECT_THAT(app_ids_, testing::ElementsAre("app1"));
+  EXPECT_THAT(app_names_, testing::ElementsAre("name1 (Windows)"));
+  EXPECT_THAT(app_vm_types_, testing::ElementsAre(PLUGIN_VM));
+}
+
 TEST_F(GuestOsFileTasksTest, PluginVm_NotEnabled) {
   fake_plugin_vm_features_.set_enabled(false);
   AddApp("app1", "name1", {}, {"txt"}, PLUGIN_VM);
diff --git a/chrome/browser/ash/guest_os/guest_os_registry_service.cc b/chrome/browser/ash/guest_os/guest_os_registry_service.cc
index 562c8d03853c87..b6f9675cccc9c7 100644
--- a/chrome/browser/ash/guest_os/guest_os_registry_service.cc
+++ b/chrome/browser/ash/guest_os/guest_os_registry_service.cc
@@ -77,12 +77,14 @@ base::Value ProtoToDictionary(const App::LocaleString& locale_string) {
   return result;
 }
 
-std::set<std::string> ListToStringSet(const base::Value* list) {
+std::set<std::string> ListToStringSet(const base::Value* list,
+                                      bool to_lower_ascii = false) {
   std::set<std::string> result;
   if (!list)
     return result;
   for (const base::Value& value : list->GetList())
-    result.insert(value.GetString());
+    result.insert(to_lower_ascii ? base::ToLowerASCII(value.GetString())
+                                 : value.GetString());
   return result;
 }
 
@@ -407,15 +409,19 @@ std::string GuestOsRegistryService::Registration::ExecutableFileName() const {
 std::set<std::string> GuestOsRegistryService::Registration::Extensions() const {
   if (pref_.is_none())
     return {};
+  // Convert to lowercase ASCII to allow case-insensitive match.
   return ListToStringSet(pref_.FindKeyOfType(guest_os::prefs::kAppExtensionsKey,
-                                             base::Value::Type::LIST));
+                                             base::Value::Type::LIST),
+                         /*to_lower_ascii=*/true);
 }
 
 std::set<std::string> GuestOsRegistryService::Registration::MimeTypes() const {
   if (pref_.is_none())
     return {};
+  // TODO(crbug.com/1258348): It may make sense for mime types to ignore case.
   return ListToStringSet(pref_.FindKeyOfType(guest_os::prefs::kAppMimeTypesKey,
-                                             base::Value::Type::LIST));
+                                             base::Value::Type::LIST),
+                         /*to_lower_ascii=*/false);
 }
 
 std::set<std::string> GuestOsRegistryService::Registration::Keywords() const {