diff --git a/pkgs/development/libraries/gtk/4.x.nix b/pkgs/development/libraries/gtk/4.x.nix
index 50b322c9dbaf..455e54ded21c 100644
--- a/pkgs/development/libraries/gtk/4.x.nix
+++ b/pkgs/development/libraries/gtk/4.x.nix
@@ -5,9 +5,7 @@
 , pkg-config
 , gettext
 , graphene
-, docbook-xsl-nons
-, docbook_xml_dtd_43
-, gtk-doc
+, gi-docgen
 , meson
 , ninja
 , python3
@@ -45,7 +43,6 @@
 , wayland-protocols
 , xineramaSupport ? stdenv.isLinux
 , cupsSupport ? stdenv.isLinux
-, withGtkDoc ? stdenv.isLinux
 , cups
 , AppKit
 , Cocoa
@@ -64,9 +61,9 @@ in
 
 stdenv.mkDerivation rec {
   pname = "gtk4";
-  version = "4.0.3";
+  version = "4.2.1";
 
-  outputs = [ "out" "dev" ] ++ lib.optional withGtkDoc "devdoc";
+  outputs = [ "out" "dev" ] ++ lib.optionals x11Support [ "devdoc" ];
   outputBin = "dev";
 
   setupHooks = [
@@ -76,7 +73,7 @@ stdenv.mkDerivation rec {
 
   src = fetchurl {
     url = "mirror://gnome/sources/gtk/${lib.versions.majorMinor version}/gtk-${version}.tar.xz";
-    sha256 = "18mJNyV5C1C9mjuyeIVtnVQ7RLa5uVHXtg573swTGJA=";
+    sha256 = "AjFpd13kPwof3gZvvBnXhUXqanViwZFavem4rkpzCeY=";
   };
 
   nativeBuildInputs = [
@@ -88,21 +85,17 @@ stdenv.mkDerivation rec {
     pkg-config
     python3
     sassc
-  ] ++ setupHooks ++ lib.optionals withGtkDoc [
-    pandoc
-    docbook_xml_dtd_43
-    docbook-xsl-nons
-    gtk-doc
-    # For xmllint
-    libxml2
-  ];
+    gi-docgen
+  ] ++ setupHooks;
 
   buildInputs = [
     libxkbcommon
     epoxy
     json-glib
     isocodes
+  ] ++ lib.optionals (!stdenv.isDarwin) [
     vulkan-headers
+  ] ++ [
     librest
     libsoup
     ffmpeg
@@ -141,18 +134,27 @@ stdenv.mkDerivation rec {
     glib
     graphene
     pango
-    vulkan-loader # TODO: Possibly not used on Darwin
-
+  ] ++ lib.optionals (!stdenv.isDarwin) [
+    vulkan-loader
+  ] ++ [
     # Required for GSettings schemas at runtime.
     # Will be picked up by wrapGAppsHook.
     gsettings-desktop-schemas
   ];
 
   mesonFlags = [
-    "-Dgtk_doc=${lib.boolToString withGtkDoc}"
-    "-Dtests=false"
-    "-Dtracker3=${lib.boolToString trackerSupport}"
-    "-Dbroadway_backend=${lib.boolToString broadwaySupport}"
+    # ../docs/tools/shooter.c:4:10: fatal error: 'cairo-xlib.h' file not found
+    "-Dgtk_doc=${lib.boolToString x11Support}"
+    "-Dbuild-tests=false"
+    "-Dtracker=${if trackerSupport then "enabled" else "disabled"}"
+    "-Dbroadway-backend=${lib.boolToString broadwaySupport}"
+  ] ++ lib.optionals (!cupsSupport) [
+    "-Dprint-cups=disabled"
+  ] ++ lib.optionals stdenv.isDarwin [
+    "-Dvulkan=disabled"
+    "-Dmedia-gstreamer=disabled" # requires gstreamer-gl
+  ] ++ lib.optionals (!x11Support) [
+    "-Dx11-backend=false"
   ];
 
   doCheck = false; # needs X11
@@ -171,20 +173,12 @@ stdenv.mkDerivation rec {
       gdk/gen-gdk-gresources-xml.py
       gtk/gen-gtk-gresources-xml.py
       gtk/gentypefuncs.py
-      docs/reference/gtk/gtk-markdown-to-docbook
     )
 
     chmod +x ''${files[@]}
     patchShebangs ''${files[@]}
   '';
 
-  postBuild =  lib.optionalString withGtkDoc ''
-    # Meson not building `custom_target`s passed to `custom_files` argument of `gnome.gtkdoc` function
-    # as part of the `install` target. We have to build the docs manually first.
-    # https://github.com/mesonbuild/meson/issues/2831
-    ninja g{t,d,s}k4-doc
-  '';
-
   preInstall = ''
     OLD_PATH="$PATH"
     PATH="$PATH:$dev/bin" # so the install script finds gtk4-update-icon-cache
@@ -202,6 +196,13 @@ stdenv.mkDerivation rec {
     for f in $dev/bin/gtk4-encode-symbolic-svg; do
       wrapProgram $f --prefix XDG_DATA_DIRS : "${shared-mime-info}/share"
     done
+
+  '' + lib.optionalString x11Support ''
+    # So that DevHelp can find this.
+    # TODO: Remove this with DevHelp 41.
+    mkdir -p "$devdoc/share/devhelp/books"
+    mv "$out/share/doc/"* "$devdoc/share/devhelp/books"
+    rmdir -p --ignore-fail-on-non-empty "$out/share/doc"
   '';
 
   # Wrap demos