diff --git a/pkgs/development/libraries/protobuf/3.21.nix b/pkgs/development/libraries/protobuf/3.21.nix
index 70c6095ae7b62..37eca85b396fb 100644
--- a/pkgs/development/libraries/protobuf/3.21.nix
+++ b/pkgs/development/libraries/protobuf/3.21.nix
@@ -1,6 +1,6 @@
 { callPackage, abseil-cpp, ... }:
 
 callPackage ./generic-v3-cmake.nix {
-  version = "3.21.2";
-  sha256 = "sha256-DUv07pWiZV7jNeSA2ClDOz9DY0x/hiJynxkbSTeJOSs=";
+  version = "3.21.5";
+  sha256 = "sha256-bWT2Bak59Ki8Zy8Lf6Gr8ByC//RpEUJ89lStHu1lnWA=";
 }
diff --git a/pkgs/development/python-modules/grpcio-tools/default.nix b/pkgs/development/python-modules/grpcio-tools/default.nix
index 4797772086ade..75c14553e73bd 100644
--- a/pkgs/development/python-modules/grpcio-tools/default.nix
+++ b/pkgs/development/python-modules/grpcio-tools/default.nix
@@ -1,4 +1,4 @@
-{ lib, buildPythonPackage, fetchPypi, protobuf, grpcio, setuptools }:
+{ lib, buildPythonPackage, fetchPypi, protobuf, grpcio, setuptools, pythonRelaxDepsHook }:
 
 buildPythonPackage rec {
   pname = "grpcio-tools";
@@ -13,6 +13,10 @@ buildPythonPackage rec {
 
   enableParallelBuilding = true;
 
+  pythonRelaxDeps = [ "protobuf" ];
+
+  nativeBuildInputs = [ pythonRelaxDepsHook ];
+
   propagatedBuildInputs = [ protobuf grpcio setuptools ];
 
   # no tests in the package
diff --git a/pkgs/development/python-modules/protobuf/default.nix b/pkgs/development/python-modules/protobuf/default.nix
index ee1d0bbffb5ab..0b6ed53e2d8b0 100644
--- a/pkgs/development/python-modules/protobuf/default.nix
+++ b/pkgs/development/python-modules/protobuf/default.nix
@@ -14,7 +14,12 @@
 }:
 
 buildPythonPackage {
-  inherit (protobuf) pname src version;
+  inherit (protobuf) pname src;
+  version =
+    if lib.versionAtLeast protobuf.version "3.21" then
+      "4.21.5" # Version source: https://github.com/protocolbuffers/protobuf/blob/v21.5/version.json#L13
+    else protobuf.version;
+
   inherit disabled;
   doCheck = doCheck && !isPy27; # setuptools>=41.4 no longer collects correctly on python2
 
diff --git a/pkgs/top-level/all-packages.nix b/pkgs/top-level/all-packages.nix
index 06a22fa16b105..18aac872d1814 100644
--- a/pkgs/top-level/all-packages.nix
+++ b/pkgs/top-level/all-packages.nix
@@ -20689,7 +20689,7 @@ with pkgs;
 
   prospector = callPackage ../development/tools/prospector { };
 
-  protobuf = protobuf3_19;
+  protobuf = protobuf3_21;
 
   protobuf3_21 = callPackage ../development/libraries/protobuf/3.21.nix { };
   protobuf3_20 = callPackage ../development/libraries/protobuf/3.20.nix { };