diff --git a/annotation/compiler/src/main/java/com/bumptech/glide/annotation/compiler/IndexerGenerator.java b/annotation/compiler/src/main/java/com/bumptech/glide/annotation/compiler/IndexerGenerator.java
index cd8038ce84..8a05c9151f 100644
--- a/annotation/compiler/src/main/java/com/bumptech/glide/annotation/compiler/IndexerGenerator.java
+++ b/annotation/compiler/src/main/java/com/bumptech/glide/annotation/compiler/IndexerGenerator.java
@@ -8,6 +8,7 @@
 import java.lang.annotation.Annotation;
 import java.util.ArrayList;
 import java.util.List;
+import java.util.UUID;
 import javax.lang.model.element.Modifier;
 import javax.lang.model.element.TypeElement;
 
@@ -46,6 +47,7 @@
  */
 final class IndexerGenerator {
   private static final String INDEXER_NAME_PREFIX = "GlideIndexer_";
+  private static final int MAXIMUM_FILE_NAME_LENGTH = 255;
   private final ProcessorUtil processorUtil;
 
   IndexerGenerator(ProcessorUtil processorUtil) {
@@ -79,7 +81,7 @@ TypeSpec generate(List<TypeElement> types) {
     }
   }
 
-  private static TypeSpec generate(
+  private TypeSpec generate(
       List<TypeElement> libraryModules, Class<? extends Annotation> annotation) {
     AnnotationSpec.Builder annotationBuilder = AnnotationSpec.builder(Index.class);
 
@@ -88,15 +90,25 @@ private static TypeSpec generate(
       annotationBuilder.addMember(value, "$S", ClassName.get(childModule).toString());
     }
 
-    StringBuilder indexerName =
+    StringBuilder indexerNameBuilder =
         new StringBuilder(INDEXER_NAME_PREFIX + annotation.getSimpleName() + "_");
     for (TypeElement element : libraryModules) {
-      indexerName.append(element.getQualifiedName().toString().replace(".", "_"));
-      indexerName.append("_");
+      indexerNameBuilder.append(element.getQualifiedName().toString().replace(".", "_"));
+      indexerNameBuilder.append("_");
+    }
+    indexerNameBuilder =
+        new StringBuilder(indexerNameBuilder.substring(0, indexerNameBuilder.length() - 1));
+    String indexerName = indexerNameBuilder.toString();
+    // If the indexer name has too many packages/modules, it can exceed the file name length
+    // allowed by the file system, which can break compilation. To avoid that, fall back to a
+    // deterministic UUID.
+    if (indexerName.length() >= (MAXIMUM_FILE_NAME_LENGTH - INDEXER_NAME_PREFIX.length())) {
+      indexerName =
+          INDEXER_NAME_PREFIX
+              + UUID.nameUUIDFromBytes(indexerName.getBytes()).toString().replace("-", "_");
     }
-    indexerName = new StringBuilder(indexerName.substring(0, indexerName.length() - 1));
 
-    return TypeSpec.classBuilder(indexerName.toString())
+    return TypeSpec.classBuilder(indexerName)
         .addAnnotation(annotationBuilder.build())
         .addModifiers(Modifier.PUBLIC)
         .build();
diff --git a/annotation/compiler/test/src/test/java/com/bumptech/glide/annotation/compiler/OverlyLongFileNameTest.java b/annotation/compiler/test/src/test/java/com/bumptech/glide/annotation/compiler/OverlyLongFileNameTest.java
new file mode 100644
index 0000000000..fa8a63d3c8
--- /dev/null
+++ b/annotation/compiler/test/src/test/java/com/bumptech/glide/annotation/compiler/OverlyLongFileNameTest.java
@@ -0,0 +1,71 @@
+package com.bumptech.glide.annotation.compiler;
+
+import static com.google.testing.compile.Compiler.javac;
+
+import com.bumptech.glide.annotation.compiler.test.CompilationProvider;
+import com.google.testing.compile.Compilation;
+import com.google.testing.compile.CompilationSubject;
+import com.google.testing.compile.JavaFileObjects;
+import java.io.File;
+import java.io.IOException;
+import javax.tools.JavaFileObject;
+import org.junit.Before;
+import org.junit.Rule;
+import org.junit.Test;
+import org.junit.rules.TemporaryFolder;
+import org.junit.runner.RunWith;
+import org.junit.runners.JUnit4;
+
+/**
+ * Makes sure that we can handle indexers based on long package or file names, or many modules.
+ *
+ * <p>See #4106.
+ */
+@RunWith(JUnit4.class)
+public class OverlyLongFileNameTest implements CompilationProvider {
+  @Rule public TemporaryFolder temporaryFolder = new TemporaryFolder();
+  private Compilation compilation;
+  private static final String FILE_NAME_LONGER_THAN_255_CHARS =
+      "SomeReallyReallyRidiculouslyLongFileNameOrPackageNameIGuessThatExceedsTwoHundredAndFiftyFive"
+          + "CharactersThoughThatsOnlyAroundOneHundredCharactersWhichMeansINeedToKeepTypingToGetTo"
+          + "TwoHundredAndFiftyFiveSomehowThankfullyOnlyLikeFiftyToGoNowMaybeButNotQuiteYet"
+          + "SomewhereAroundNowIsProbablyGood";
+
+  @Before
+  public void setUp() {
+    compilation =
+        javac()
+            .withProcessors(new GlideAnnotationProcessor())
+            .compile(
+                JavaFileObjects.forSourceLines(
+                    FILE_NAME_LONGER_THAN_255_CHARS,
+                    "package com.bumptech.glide.test;",
+                    "import com.bumptech.glide.annotation.GlideModule;",
+                    "import com.bumptech.glide.module.LibraryGlideModule;",
+                    "@GlideModule",
+                    "public final class "
+                        + FILE_NAME_LONGER_THAN_255_CHARS
+                        + " extends LibraryGlideModule {}"));
+  }
+
+  @Test
+  public void compilingLongClassAndOrPackageNameShouldSucceed() throws IOException {
+    CompilationSubject.assertThat(compilation).succeededWithoutWarnings();
+    for (JavaFileObject file : compilation.generatedFiles()) {
+      temporaryFolder.create();
+      String actualFileName = new File(file.getName()).getName();
+      if (!actualFileName.startsWith(FILE_NAME_LONGER_THAN_255_CHARS)) {
+        try {
+          temporaryFolder.newFile(actualFileName).createNewFile();
+        } catch (IOException e) {
+          throw new RuntimeException("Failed to create: " + actualFileName, e);
+        }
+      }
+    }
+  }
+
+  @Override
+  public Compilation getCompilation() {
+    return compilation;
+  }
+}