diff --git a/crates/uv-cli/src/lib.rs b/crates/uv-cli/src/lib.rs
index 8324d5f8701b..610717bee953 100644
--- a/crates/uv-cli/src/lib.rs
+++ b/crates/uv-cli/src/lib.rs
@@ -2702,7 +2702,7 @@ pub struct RunArgs {
     /// Run a Python module.
     ///
     /// Equivalent to `python -m <module>`.
-    #[arg(short, long, conflicts_with = "script")]
+    #[arg(short, long, conflicts_with_all = ["script", "gui_script"])]
     pub module: bool,
 
     /// Only include the development dependency group.
@@ -2801,9 +2801,16 @@ pub struct RunArgs {
     ///
     /// Using `--script` will attempt to parse the path as a PEP 723 script,
     /// irrespective of its extension.
-    #[arg(long, short, conflicts_with = "module")]
+    #[arg(long, short, conflicts_with_all = ["module", "gui_script"])]
     pub script: bool,
 
+    /// Run the given path as a Python GUI script.
+    ///
+    /// Using `--gui-script` will attempt to parse the path as a PEP 723 script and run it with pythonw.exe,
+    /// irrespective of its extension. Only available on Windows.
+    #[arg(long, conflicts_with_all = ["script", "module"])]
+    pub gui_script: bool,
+
     #[command(flatten)]
     pub installer: ResolverInstallerArgs,
 
diff --git a/crates/uv/src/commands/project/run.rs b/crates/uv/src/commands/project/run.rs
index 165709c11116..2ac15cc25c5f 100644
--- a/crates/uv/src/commands/project/run.rs
+++ b/crates/uv/src/commands/project/run.rs
@@ -1344,10 +1344,12 @@ impl std::fmt::Display for RunCommand {
 
 impl RunCommand {
     /// Determine the [`RunCommand`] for a given set of arguments.
+    #[allow(clippy::fn_params_excessive_bools)]
     pub(crate) async fn from_args(
         command: &ExternalCommand,
         module: bool,
         script: bool,
+        gui_script: bool,
         connectivity: Connectivity,
         native_tls: bool,
         allow_insecure_host: &[TrustedHost],
@@ -1401,6 +1403,11 @@ impl RunCommand {
             return Ok(Self::PythonModule(target.clone(), args.to_vec()));
         } else if script {
             return Ok(Self::PythonScript(target.clone().into(), args.to_vec()));
+        } else if gui_script {
+            if cfg!(windows) {
+                return Ok(Self::PythonGuiScript(target.clone().into(), args.to_vec()));
+            }
+            anyhow::bail!("`--gui-script` is only supported on Windows. Did you mean `--script`?");
         }
 
         let metadata = target_path.metadata();
diff --git a/crates/uv/src/lib.rs b/crates/uv/src/lib.rs
index f6ffefe8ac6c..c3a76abd5950 100644
--- a/crates/uv/src/lib.rs
+++ b/crates/uv/src/lib.rs
@@ -141,6 +141,7 @@ async fn run(mut cli: Cli) -> Result<ExitStatus> {
             command: Some(command),
             module,
             script,
+            gui_script,
             ..
         }) = &mut **command
         {
@@ -150,6 +151,7 @@ async fn run(mut cli: Cli) -> Result<ExitStatus> {
                     command,
                     *module,
                     *script,
+                    *gui_script,
                     settings.connectivity,
                     settings.native_tls,
                     &settings.allow_insecure_host,
diff --git a/crates/uv/src/settings.rs b/crates/uv/src/settings.rs
index cd8d705930ac..6c6535d26f9d 100644
--- a/crates/uv/src/settings.rs
+++ b/crates/uv/src/settings.rs
@@ -296,6 +296,7 @@ impl RunSettings {
             only_dev,
             no_editable,
             script: _,
+            gui_script: _,
             command: _,
             with,
             with_editable,
diff --git a/crates/uv/tests/it/run.rs b/crates/uv/tests/it/run.rs
index 5f758bb4e13f..4f20d6c3af58 100644
--- a/crates/uv/tests/it/run.rs
+++ b/crates/uv/tests/it/run.rs
@@ -2893,6 +2893,68 @@ fn run_script_explicit_directory() -> Result<()> {
     Ok(())
 }
 
+#[test]
+#[cfg(windows)]
+fn run_gui_script_explicit() -> Result<()> {
+    let context = TestContext::new("3.12");
+
+    let test_script = context.temp_dir.child("script");
+    test_script.write_str(indoc! { r#"
+        # /// script
+        # requires-python = ">=3.11"
+        # dependencies = []
+        # ///
+        import sys
+        import os
+
+        executable = os.path.basename(sys.executable).lower()
+        if not executable.startswith("pythonw"):
+            print(f"Error: Expected pythonw.exe but got: {executable}", file=sys.stderr)
+            sys.exit(1)
+        
+        print(f"Using executable: {executable}", file=sys.stderr)
+    "#})?;
+
+    uv_snapshot!(context.filters(), context.run().arg("--gui-script").arg("script"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+
+    ----- stderr -----
+    Reading inline script metadata from `script`
+    Resolved in [TIME]
+    Audited in [TIME]
+    Using executable: pythonw.exe
+    "###);
+
+    Ok(())
+}
+
+#[test]
+#[cfg(not(windows))]
+fn run_gui_script_not_supported() -> Result<()> {
+    let context = TestContext::new("3.12");
+    let test_script = context.temp_dir.child("script");
+    test_script.write_str(indoc! { r#"
+        # /// script
+        # requires-python = ">=3.11"
+        # dependencies = []
+        # ///
+        print("Hello")
+    "#})?;
+
+    uv_snapshot!(context.filters(), context.run().arg("--gui-script").arg("script"), @r###"
+    success: false
+    exit_code: 2
+    ----- stdout -----
+
+    ----- stderr -----
+    error: `--gui-script` is only supported on Windows. Did you mean `--script`?
+    "###);
+
+    Ok(())
+}
+
 #[test]
 fn run_remote_pep723_script() {
     let context = TestContext::new("3.12").with_filtered_python_names();
diff --git a/docs/reference/cli.md b/docs/reference/cli.md
index 6878535f4aa8..eda25f29a74c 100644
--- a/docs/reference/cli.md
+++ b/docs/reference/cli.md
@@ -184,6 +184,10 @@ uv run [OPTIONS] [COMMAND]
 
 <p>May be provided multiple times.</p>
 
+</dd><dt><code>--gui-script</code></dt><dd><p>Run the given path as a Python GUI script.</p>
+
+<p>Using <code>--gui-script</code> will attempt to parse the path as a PEP 723 script and run it with pythonw.exe, irrespective of its extension. Only available on Windows.</p>
+
 </dd><dt><code>--help</code>, <code>-h</code></dt><dd><p>Display the concise help for this command</p>
 
 </dd><dt><code>--index</code> <i>index</i></dt><dd><p>The URLs to use when resolving dependencies, in addition to the default index.</p>