diff --git a/CHANGELOG.md b/CHANGELOG.md
index e64c196b2041..7ba96dab57b9 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -10,6 +10,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 ### Fixed
 
 - Don't rely on `@layer base` for the `@property` polyfills ([#17506](https://github.com/tailwindlabs/tailwindcss/pull/17506))
+- Fix multi-value inset shadow ([#17523](https://github.com/tailwindlabs/tailwindcss/pull/17523))
 
 ## [4.1.1] - 2025-04-02
 
diff --git a/packages/tailwindcss/src/utilities.test.ts b/packages/tailwindcss/src/utilities.test.ts
index be5becf61027..fd75f6a94919 100644
--- a/packages/tailwindcss/src/utilities.test.ts
+++ b/packages/tailwindcss/src/utilities.test.ts
@@ -23263,11 +23263,13 @@ test('inset-shadow', async () => {
         'inset-shadow-[10px_10px]',
         'inset-shadow-[var(--value)]',
         'inset-shadow-[shadow:var(--value)]',
+        'inset-shadow-[12px_12px_#0088cc,12px_12px_var(--value,#0088cc)]',
 
         'inset-shadow-sm/25',
         'inset-shadow-[12px_12px_#0088cc]/25',
         'inset-shadow-[12px_12px_var(--value)]/25',
         'inset-shadow-[10px_10px]/25',
+        'inset-shadow-[12px_12px_#0088cc,12px_12px_var(--value,#0088cc)]/25',
 
         // Colors
         'inset-shadow-red-500',
@@ -23319,6 +23321,18 @@ test('inset-shadow', async () => {
       --color-red-500: #ef4444;
     }
 
+    .inset-shadow-\\[12px_12px_\\#0088cc\\,12px_12px_var\\(--value\\,\\#0088cc\\)\\]\\/25 {
+      --tw-inset-shadow-alpha: 25%;
+      --tw-inset-shadow: inset 12px 12px var(--tw-inset-shadow-color, #08c), inset 12px 12px var(--tw-inset-shadow-color, var(--value, #08c));
+      box-shadow: var(--tw-inset-shadow), var(--tw-inset-ring-shadow), var(--tw-ring-offset-shadow), var(--tw-ring-shadow), var(--tw-shadow);
+    }
+
+    @supports (color: lab(from red l a b)) {
+      .inset-shadow-\\[12px_12px_\\#0088cc\\,12px_12px_var\\(--value\\,\\#0088cc\\)\\]\\/25 {
+        --tw-inset-shadow: inset 12px 12px var(--tw-inset-shadow-color, oklab(59.9824% -.067 -.124 / .25)), inset 12px 12px var(--tw-inset-shadow-color, oklab(from var(--value, #08c) l a b / 25%));
+      }
+    }
+
     .inset-shadow-\\[12px_12px_var\\(--value\\)\\]\\/25 {
       --tw-inset-shadow-alpha: 25%;
       --tw-inset-shadow: inset 12px 12px var(--tw-inset-shadow-color, var(--value));
@@ -23359,6 +23373,11 @@ test('inset-shadow', async () => {
       box-shadow: var(--tw-inset-shadow), var(--tw-inset-ring-shadow), var(--tw-ring-offset-shadow), var(--tw-ring-shadow), var(--tw-shadow);
     }
 
+    .inset-shadow-\\[12px_12px_\\#0088cc\\,12px_12px_var\\(--value\\,\\#0088cc\\)\\] {
+      --tw-inset-shadow: inset 12px 12px var(--tw-inset-shadow-color, #08c), inset 12px 12px var(--tw-inset-shadow-color, var(--value, #08c));
+      box-shadow: var(--tw-inset-shadow), var(--tw-inset-ring-shadow), var(--tw-ring-offset-shadow), var(--tw-ring-shadow), var(--tw-shadow);
+    }
+
     .inset-shadow-\\[12px_12px_\\#0088cc\\] {
       --tw-inset-shadow: inset 12px 12px var(--tw-inset-shadow-color, #08c);
       box-shadow: var(--tw-inset-shadow), var(--tw-inset-ring-shadow), var(--tw-ring-offset-shadow), var(--tw-ring-shadow), var(--tw-shadow);
diff --git a/packages/tailwindcss/src/utilities.ts b/packages/tailwindcss/src/utilities.ts
index a4359c53a1ab..88f9a1fbc13b 100644
--- a/packages/tailwindcss/src/utilities.ts
+++ b/packages/tailwindcss/src/utilities.ts
@@ -6183,13 +6183,20 @@ function alphaReplacedShadowProperties(
     return varInjector(replaceAlpha(color, alpha))
   })
 
+  function applyPrefix(x: string) {
+    if (!prefix) return x
+    return segment(x, ',')
+      .map((value) => prefix + value)
+      .join(',')
+  }
+
   if (requiresFallback) {
     return [
-      decl(property, prefix + replaceShadowColors(value, varInjector)),
-      rule('@supports (color: lab(from red l a b))', [decl(property, prefix + replacedValue)]),
+      decl(property, applyPrefix(replaceShadowColors(value, varInjector))),
+      rule('@supports (color: lab(from red l a b))', [decl(property, applyPrefix(replacedValue))]),
     ]
   } else {
-    return [decl(property, prefix + replacedValue)]
+    return [decl(property, applyPrefix(replacedValue))]
   }
 }