diff --git a/packages/react-native/src/private/webapis/structuredClone/__tests__/structuredClone-test.js b/packages/react-native/src/private/webapis/structuredClone/__tests__/structuredClone-test.js
new file mode 100644
index 000000000000..32f2c32443a2
--- /dev/null
+++ b/packages/react-native/src/private/webapis/structuredClone/__tests__/structuredClone-test.js
@@ -0,0 +1,57 @@
+/**
+ * Copyright (c) Meta Platforms, Inc. and affiliates.
+ *
+ * This source code is licensed under the MIT license found in the
+ * LICENSE file in the root directory of this source tree.
+ *
+ * @flow strict-local
+ * @format
+ */
+
+import DOMException from '../../errors/DOMException';
+
+// Snapshot the built-in prototypes before the first evaluation of the
+// module under test. `structuredClone` is required (not imported) below so
+// its top-level code runs after this snapshot, which is what lets the
+// no-mutation regression test detect writes to the built-in prototypes.
+const PROTOTYPE_SYMBOLS = {
+  WeakMap: Object.getOwnPropertySymbols(WeakMap.prototype),
+  WeakSet: Object.getOwnPropertySymbols(WeakSet.prototype),
+  Promise: Object.getOwnPropertySymbols(Promise.prototype),
+};
+
+function expectDataCloneError(fn: () => unknown) {
+  try {
+    fn();
+  } catch (error) {
+    expect(error).toBeInstanceOf(DOMException);
+    expect(error.name).toBe('DataCloneError');
+    return;
+  }
+
+  throw new Error('Expected function to throw DataCloneError, but it did not');
+}
+
+describe('structuredClone', () => {
+  it('does not add properties to built-in prototypes', () => {
+    require('../structuredClone');
+
+    expect(Object.getOwnPropertySymbols(WeakMap.prototype)).toEqual(
+      PROTOTYPE_SYMBOLS.WeakMap,
+    );
+    expect(Object.getOwnPropertySymbols(WeakSet.prototype)).toEqual(
+      PROTOTYPE_SYMBOLS.WeakSet,
+    );
+    expect(Object.getOwnPropertySymbols(Promise.prototype)).toEqual(
+      PROTOTYPE_SYMBOLS.Promise,
+    );
+  });
+
+  it('throws DataCloneError for non-serializable built-ins', () => {
+    const {default: structuredClone} = require('../structuredClone');
+
+    expectDataCloneError(() => structuredClone(new WeakMap()));
+    expectDataCloneError(() => structuredClone(new WeakSet()));
+    expectDataCloneError(() => structuredClone(new Promise(() => {})));
+  });
+});
diff --git a/packages/react-native/src/private/webapis/structuredClone/structuredClone.js b/packages/react-native/src/private/webapis/structuredClone/structuredClone.js
index 820534ef2a57..ef64df93f736 100644
--- a/packages/react-native/src/private/webapis/structuredClone/structuredClone.js
+++ b/packages/react-native/src/private/webapis/structuredClone/structuredClone.js
@@ -295,8 +295,6 @@ export default function structuredClone<T>(value: T): T {
   }
 }
 
-const NON_SERIALIZABLE_OBJECT_KEY = Symbol('nonSerializableObject');
-
 function cloneArrayBuffer(value: ArrayBuffer): ArrayBuffer {
   const existingClone = memory.get(value);
   if (existingClone instanceof ArrayBuffer) {
@@ -392,16 +390,11 @@ function createErrorClone(value: Error): Error {
 }
 
 function isNonSerializableObject<T extends interface {}>(obj: T): boolean {
-  // $FlowExpectedError[invalid-in-lhs]
-  return NON_SERIALIZABLE_OBJECT_KEY in obj;
-}
-
-function markClassAsNonSerializable<T>(cls: Class<T>): void {
-  // $FlowExpectedError[incompatible-use]
-  cls.prototype[NON_SERIALIZABLE_OBJECT_KEY] = true;
+  // Built-in prototypes must not be written to because Hardened JS
+  // environments (SES) freeze them, so the non-serializable
+  // built-ins are detected with `instanceof` instead of marking the
+  // prototypes with e.g. Symbol('nonSerializableObject').
+  return (
+    obj instanceof WeakMap || obj instanceof WeakSet || obj instanceof Promise
+  );
 }
-
-// Non-serializable built-ins.
-markClassAsNonSerializable(WeakMap);
-markClassAsNonSerializable(WeakSet);
-markClassAsNonSerializable(Promise);