diff --git a/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/ConfigurableHintsRegistrationProcessor.java b/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/ConfigurableHintsRegistrationProcessor.java
index 9dc0f733f..ec3847b59 100644
--- a/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/ConfigurableHintsRegistrationProcessor.java
+++ b/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/ConfigurableHintsRegistrationProcessor.java
@@ -70,7 +70,7 @@ class ConfigurableHintsRegistrationProcessor implements BeanFactoryInitializatio
 			Set.of("org.springframework.security.oauth2.client.OAuth2AuthorizedClient",
 					"org.springframework.security.web.server.SecurityWebFilterChain",
 					"org.springframework.boot.security.autoconfigure.SecurityProperties"),
-			JsonToGrpcGatewayFilterFactory.class, Set.of("io.grpc.Channel"), RedisRateLimiter.class,
+			JsonToGrpcGatewayFilterFactory.class, Set.of("io.grpc.netty.NettyChannelBuilder"), RedisRateLimiter.class,
 			Set.of("org.springframework.data.redis.core.RedisTemplate",
 					"org.springframework.web.reactive.DispatcherHandler"),
 			SpringCloudCircuitBreakerResilience4JFilterFactory.class, circuitBreakerConditionalClasses,
diff --git a/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/GatewayAutoConfiguration.java b/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/GatewayAutoConfiguration.java
index b1e2f60fd..f45953ebd 100644
--- a/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/GatewayAutoConfiguration.java
+++ b/spring-cloud-gateway-server-webflux/src/main/java/org/springframework/cloud/gateway/config/GatewayAutoConfiguration.java
@@ -370,7 +370,7 @@ public GRPCResponseHeadersFilter gRPCResponseHeadersFilter() {
 	@Bean
 	@ConditionalOnEnabledFilter
 	@ConditionalOnProperty(name = "server.http2.enabled", matchIfMissing = true)
-	@ConditionalOnClass(name = "io.grpc.Channel")
+	@ConditionalOnClass(name = "io.grpc.netty.NettyChannelBuilder")
 	public JsonToGrpcGatewayFilterFactory jsonToGRPCFilterFactory(GrpcSslConfigurer gRPCSSLContext,
 			ResourceLoader resourceLoader) {
 		return new JsonToGrpcGatewayFilterFactory(gRPCSSLContext, resourceLoader);
@@ -379,7 +379,7 @@ public JsonToGrpcGatewayFilterFactory jsonToGRPCFilterFactory(GrpcSslConfigurer
 	@Bean
 	@ConditionalOnEnabledFilter(JsonToGrpcGatewayFilterFactory.class)
 	@ConditionalOnMissingBean(GrpcSslConfigurer.class)
-	@ConditionalOnClass(name = "io.grpc.Channel")
+	@ConditionalOnClass(name = "io.grpc.netty.NettyChannelBuilder")
 	public GrpcSslConfigurer grpcSslConfigurer(HttpClientProperties properties, SslBundles bundles)
 			throws KeyStoreException, NoSuchAlgorithmException, CertificateException, IOException {
 		TrustManagerFactory trustManagerFactory = TrustManagerFactory
diff --git a/spring-cloud-gateway-server-webflux/src/test/java/org/springframework/cloud/gateway/config/GatewayAutoConfigurationTests.java b/spring-cloud-gateway-server-webflux/src/test/java/org/springframework/cloud/gateway/config/GatewayAutoConfigurationTests.java
index 095066d68..346b02c80 100644
--- a/spring-cloud-gateway-server-webflux/src/test/java/org/springframework/cloud/gateway/config/GatewayAutoConfigurationTests.java
+++ b/spring-cloud-gateway-server-webflux/src/test/java/org/springframework/cloud/gateway/config/GatewayAutoConfigurationTests.java
@@ -57,6 +57,7 @@
 import org.springframework.cloud.gateway.actuate.GatewayLegacyControllerEndpoint;
 import org.springframework.cloud.gateway.config.GatewayAutoConfigurationTests.CustomHttpClientFactory.CustomSslConfigurer;
 import org.springframework.cloud.gateway.config.HttpClientProperties.Pool.LeasingStrategy;
+import org.springframework.cloud.gateway.filter.factory.JsonToGrpcGatewayFilterFactory;
 import org.springframework.cloud.gateway.filter.factory.TokenRelayGatewayFilterFactory;
 import org.springframework.cloud.gateway.filter.headers.ForwardedHeadersFilter;
 import org.springframework.cloud.gateway.filter.headers.GRPCRequestHeadersFilter;
@@ -315,6 +316,26 @@ public void gRPCFiltersNotConfiguredWhenHTTP2Disabled() {
 			});
 	}
 
+	@Test // gh-4169
+	public void grpcBeansNotConfiguredWhenGrpcNettyAbsent() {
+		// io.grpc.Channel comes from grpc-api, but the gRPC beans require grpc-netty
+		// (io.grpc.netty.NettyChannelBuilder). When grpc-api is present without
+		// grpc-netty the beans must back off rather than fail the context with
+		// NoClassDefFoundError: io/grpc/netty/NettyChannelBuilder.
+		new ReactiveWebApplicationContextRunner()
+			.withClassLoader(
+					new org.springframework.boot.test.context.FilteredClassLoader("io.grpc.netty.NettyChannelBuilder"))
+			.withConfiguration(AutoConfigurations.of(WebFluxAutoConfiguration.class, MetricsAutoConfiguration.class,
+					SimpleMetricsExportAutoConfiguration.class, GatewayAutoConfiguration.class,
+					HttpClientCustomizedConfig.class, ServerPropertiesConfig.class))
+			.withPropertyValues("server.http2.enabled=true")
+			.run(context -> {
+				assertThat(context).hasNotFailed();
+				assertThat(context).doesNotHaveBean(JsonToGrpcGatewayFilterFactory.class);
+				assertThat(context).doesNotHaveBean(GrpcSslConfigurer.class);
+			});
+	}
+
 	@Test
 	public void insecureTrustManagerNotEnabledByDefaultWhenHTTP2Enabled() {
 		new ReactiveWebApplicationContextRunner()