diff --git a/README.md b/README.md
index d96549dcd..45c4b7ce7 100644
--- a/README.md
+++ b/README.md
@@ -302,7 +302,7 @@ const { data: app } = await requestWithAuth(
   <tr>
     <th align=left>
       <a name="options-request-agent"></a>
-      <code>options.request.agent</code>
+      <code>options.request.agent</code> (node-fetch only)
     </th>
     <td>
       <a href="https://nodejs.org/api/http.html#http_class_http_agent">http(s).Agent</a> instance
diff --git a/src/fetch-wrapper.ts b/src/fetch-wrapper.ts
index 2158fdc3a..fa67c6d09 100644
--- a/src/fetch-wrapper.ts
+++ b/src/fetch-wrapper.ts
@@ -36,6 +36,17 @@ export default function fetchWrapper(
     );
   }
 
+  if (
+    typeof globalThis.fetch !== "undefined" &&
+    typeof requestOptions.request?.agent !== "undefined"
+  ) {
+    throw new Error(
+      `Global "fetch" and "agent" options cannot be used together,
+      please use a custom fetch function with the "dispatcher" option,
+      or use "node-fetch" instead. See https://github.com/octokit/octokit.js/discussions/2484`
+    );
+  }
+
   return fetch(
     requestOptions.url,
     Object.assign(