diff --git a/Library/Homebrew/cleanup.rb b/Library/Homebrew/cleanup.rb
index 716a23dfbb..deadc6bd53 100644
--- a/Library/Homebrew/cleanup.rb
+++ b/Library/Homebrew/cleanup.rb
@@ -235,6 +235,7 @@ module Homebrew
         cleanup_cache
         cleanup_logs
         cleanup_lockfiles
+        cleanup_python_site_packages
         prune_prefix_symlinks_and_directories
 
         unless dry_run?
@@ -484,6 +485,55 @@ module Homebrew
           end
     end
 
+    def cleanup_python_site_packages
+      pyc_files = Hash.new { |h, k| h[k] = [] }
+      seen_non_pyc_file = Hash.new { |h, k| h[k] = false }
+      unused_pyc_files = []
+
+      HOMEBREW_PREFIX.glob("lib/python*/site-packages").each do |site_packages|
+        site_packages.each_child do |child|
+          next unless child.directory?
+          # TODO: Work out a sensible way to clean up pip's, setuptools', and wheel's
+          #       {dist,site}-info directories. Alternatively, consider always removing
+          #       all `-info` directories, because we may not be making use of them.
+          next if child.basename.to_s.end_with?("-info")
+
+          # Clean up old *.pyc files in the top-level __pycache__.
+          if child.basename.to_s == "__pycache__"
+            child.find do |path|
+              next unless path.extname == ".pyc"
+              next unless path.prune?(days)
+
+              unused_pyc_files << path
+            end
+
+            next
+          end
+
+          # Look for directories that contain only *.pyc files.
+          child.find do |path|
+            next if path.directory?
+
+            if path.extname == ".pyc"
+              pyc_files[child] << path
+            else
+              seen_non_pyc_file[child] = true
+              break
+            end
+          end
+        end
+      end
+
+      unused_pyc_files += pyc_files.reject { |k,| seen_non_pyc_file[k] }
+                                   .values
+                                   .flatten
+      return if unused_pyc_files.blank?
+
+      unused_pyc_files.each do |pyc|
+        cleanup_path(pyc) { pyc.unlink }
+      end
+    end
+
     def prune_prefix_symlinks_and_directories
       ObserverPathnameExtension.reset_counts!
 
diff --git a/Library/Homebrew/test/cleanup_spec.rb b/Library/Homebrew/test/cleanup_spec.rb
index 477de25fcd..007b64753e 100644
--- a/Library/Homebrew/test/cleanup_spec.rb
+++ b/Library/Homebrew/test/cleanup_spec.rb
@@ -364,4 +364,41 @@ describe Homebrew::Cleanup do
       end
     end
   end
+
+  describe "::cleanup_python_site_packages" do
+    context "when cleaning up Python modules" do
+      let(:foo_module) { (HOMEBREW_PREFIX/"lib/python3.99/site-packages/foo") }
+      let(:foo_pycache) { (foo_module/"__pycache__") }
+      let(:foo_pyc) { (foo_pycache/"foo.cypthon-399.pyc") }
+
+      before do
+        foo_pycache.mkpath
+        FileUtils.touch foo_pyc
+      end
+
+      it "cleans up stray `*.pyc` files" do
+        cleanup.cleanup_python_site_packages
+        expect(foo_pyc).not_to exist
+      end
+
+      it "retains `*.pyc` files of installed modules" do
+        FileUtils.touch foo_module/"__init__.py"
+
+        cleanup.cleanup_python_site_packages
+        expect(foo_pyc).to exist
+      end
+    end
+
+    it "cleans up stale `*.pyc` files in the top-level `__pycache__`" do
+      pycache = HOMEBREW_PREFIX/"lib/python3.99/site-packages/__pycache__"
+      foo_pyc = pycache/"foo.cypthon-3.99.pyc"
+      pycache.mkpath
+      FileUtils.touch foo_pyc
+
+      allow_any_instance_of(Pathname).to receive(:ctime).and_return(Time.now - (2 * 60 * 60 * 24))
+      allow_any_instance_of(Pathname).to receive(:mtime).and_return(Time.now - (2 * 60 * 60 * 24))
+      described_class.new(days: 1).cleanup_python_site_packages
+      expect(foo_pyc).not_to exist
+    end
+  end
 end