diff --git a/packages/playground/define/__tests__/define.spec.ts b/packages/playground/define/__tests__/define.spec.ts
index ef8ac0b2de61b4..b359434a859d2c 100644
--- a/packages/playground/define/__tests__/define.spec.ts
+++ b/packages/playground/define/__tests__/define.spec.ts
@@ -11,4 +11,7 @@ test('string', async () => {
   expect(await page.textContent('.env-var')).toBe(
     JSON.parse(defines['process.env.SOMEVAR'])
   )
+  expect(await page.textContent('.process-as-property')).toBe(
+    defines.__OBJ__.process.env.SOMEVAR
+  )
 })
diff --git a/packages/playground/define/index.html b/packages/playground/define/index.html
index d948e7687e805d..80ecf11c9f851b 100644
--- a/packages/playground/define/index.html
+++ b/packages/playground/define/index.html
@@ -6,6 +6,7 @@ <h1>Define</h1>
 <p>Boolean <code class="boolean"></code></p>
 <p>Object <span class="pre object"></span></p>
 <p>Env Var <code class="env-var"></code></p>
+<p>process as property: <code class="process-as-property"></code></p>
 
 <script type="module">
   text('.exp', __EXP__)
@@ -14,6 +15,7 @@ <h1>Define</h1>
   text('.boolean', __BOOLEAN__)
   text('.object', JSON.stringify(__OBJ__, null, 2))
   text('.env-var', process.env.SOMEVAR)
+  text('.process-as-property', __OBJ__.process.env.SOMEVAR)
 
   function text(el, text) {
     document.querySelector(el).textContent = text
diff --git a/packages/playground/define/vite.config.js b/packages/playground/define/vite.config.js
index efca6566a19c76..422f1c4daa9628 100644
--- a/packages/playground/define/vite.config.js
+++ b/packages/playground/define/vite.config.js
@@ -8,6 +8,11 @@ module.exports = {
       foo: 1,
       bar: {
         baz: 2
+      },
+      process: {
+        env: {
+          SOMEVAR: '"PROCESS MAY BE PROPERTY"'
+        }
       }
     },
     'process.env.SOMEVAR': '"SOMEVAR"'
diff --git a/packages/vite/src/node/plugins/define.ts b/packages/vite/src/node/plugins/define.ts
index 573c0d362c46c7..7bc8f5ecfd5c90 100644
--- a/packages/vite/src/node/plugins/define.ts
+++ b/packages/vite/src/node/plugins/define.ts
@@ -32,13 +32,21 @@ export function definePlugin(config: ResolvedConfig): Plugin {
 
   const replacements: Record<string, string | undefined> = {
     'process.env.NODE_ENV': JSON.stringify(process.env.NODE_ENV || config.mode),
+    'global.process.env.NODE_ENV': JSON.stringify(
+      process.env.NODE_ENV || config.mode
+    ),
+    'globalThis.process.env.NODE_ENV': JSON.stringify(
+      process.env.NODE_ENV || config.mode
+    ),
     ...userDefine,
     ...importMetaKeys,
-    'process.env.': `({}).`
+    'process.env.': `({}).`,
+    'global.process.env.': `({}).`,
+    'globalThis.process.env.': `({}).`
   }
 
   const pattern = new RegExp(
-    '\\b(' +
+    '(?<!\\.)\\b(' +
       Object.keys(replacements)
         .map((str) => {
           return str.replace(/[-[\]/{}()*+?.\\^$|]/g, '\\$&')