diff --git a/crates/uv-build/src/lib.rs b/crates/uv-build/src/lib.rs
index 969938714..c61108054 100644
--- a/crates/uv-build/src/lib.rs
+++ b/crates/uv-build/src/lib.rs
@@ -28,7 +28,7 @@ use tracing::{debug, info_span, instrument, Instrument};
 use distribution_types::Resolution;
 use pep440_rs::{Version, VersionSpecifiers};
 use pep508_rs::Requirement;
-use uv_fs::Simplified;
+use uv_fs::{PythonExt, Simplified};
 use uv_interpreter::{Interpreter, PythonEnvironment};
 use uv_traits::{
     BuildContext, BuildIsolation, BuildKind, ConfigSettings, SetupPyStrategy, SourceBuildTrait,
@@ -637,7 +637,7 @@ impl SourceBuild {
             pep517_backend.backend_import(),
             escape_path_for_python(&metadata_directory),
             self.config_settings.escape_for_python(),
-            escape_path_for_python(&outfile),
+            outfile.escape_for_python(),
         };
         let span = info_span!(
             "run_python_script",
@@ -744,7 +744,7 @@ impl SourceBuild {
             .metadata_directory
             .as_deref()
             .map_or("None".to_string(), |path| {
-                format!(r#""{}""#, escape_path_for_python(path))
+                format!(r#""{}""#, path.escape_for_python())
             });
 
         // Write the hook output to a file so that we can read it back reliably.
@@ -767,10 +767,10 @@ impl SourceBuild {
             "#,
             pep517_backend.backend_import(),
             self.build_kind,
-            escape_path_for_python(wheel_dir),
+            wheel_dir.escape_for_python(),
             metadata_directory,
             self.config_settings.escape_for_python(),
-            escape_path_for_python(&outfile)
+            outfile.escape_for_python()
         };
         let span = info_span!(
             "run_python_script",
@@ -869,7 +869,7 @@ async fn create_pep517_build_environment(
         pep517_backend.backend_import(),
         build_kind,
         config_settings.escape_for_python(),
-        escape_path_for_python(&outfile)
+        outfile.escape_for_python()
     };
     let span = info_span!(
         "run_python_script",
diff --git a/crates/uv-fs/src/path.rs b/crates/uv-fs/src/path.rs
index d722fb41e..521ae86db 100644
--- a/crates/uv-fs/src/path.rs
+++ b/crates/uv-fs/src/path.rs
@@ -24,6 +24,20 @@ impl<T: AsRef<Path>> Simplified for T {
     }
 }
 
+pub trait PythonExt {
+    /// Escape a [`Path`] for use in Python code.
+    fn escape_for_python(&self) -> String;
+}
+
+impl<T: AsRef<Path>> PythonExt for T {
+    fn escape_for_python(&self) -> String {
+        self.as_ref()
+            .to_string_lossy()
+            .replace('\\', "\\\\")
+            .replace('"', "\\\"")
+    }
+}
+
 /// Normalize the `path` component of a URL for use as a file path.
 ///
 /// For example, on Windows, transforms `C:\Users\ferris\wheel-0.42.0.tar.gz` to
diff --git a/crates/uv-interpreter/python/get_interpreter_info.py b/crates/uv-interpreter/python/get_interpreter_info.py
index 47a70ccc6..3a8917c9e 100644
--- a/crates/uv-interpreter/python/get_interpreter_info.py
+++ b/crates/uv-interpreter/python/get_interpreter_info.py
@@ -498,30 +498,35 @@ def get_operating_system_and_architecture():
     return {"os": operating_system, "arch": architecture}
 
 
-markers = {
-    "implementation_name": implementation_name,
-    "implementation_version": implementation_version,
-    "os_name": os.name,
-    "platform_machine": platform.machine(),
-    "platform_python_implementation": platform.python_implementation(),
-    "platform_release": platform.release(),
-    "platform_system": platform.system(),
-    "platform_version": platform.version(),
-    "python_full_version": python_full_version,
-    "python_version": ".".join(platform.python_version_tuple()[:2]),
-    "sys_platform": sys.platform,
-}
-interpreter_info = {
-    "result": "success",
-    "markers": markers,
-    "base_prefix": sys.base_prefix,
-    "base_exec_prefix": sys.base_exec_prefix,
-    "prefix": sys.prefix,
-    "base_executable": getattr(sys, "_base_executable", None),
-    "sys_executable": sys.executable,
-    "stdlib": sysconfig.get_path("stdlib"),
-    "scheme": get_scheme(),
-    "virtualenv": get_virtualenv(),
-    "platform": get_operating_system_and_architecture(),
-}
-print(json.dumps(interpreter_info))
+def main() -> None:
+    markers = {
+        "implementation_name": implementation_name,
+        "implementation_version": implementation_version,
+        "os_name": os.name,
+        "platform_machine": platform.machine(),
+        "platform_python_implementation": platform.python_implementation(),
+        "platform_release": platform.release(),
+        "platform_system": platform.system(),
+        "platform_version": platform.version(),
+        "python_full_version": python_full_version,
+        "python_version": ".".join(platform.python_version_tuple()[:2]),
+        "sys_platform": sys.platform,
+    }
+    interpreter_info = {
+        "result": "success",
+        "markers": markers,
+        "base_prefix": sys.base_prefix,
+        "base_exec_prefix": sys.base_exec_prefix,
+        "prefix": sys.prefix,
+        "base_executable": getattr(sys, "_base_executable", None),
+        "sys_executable": sys.executable,
+        "stdlib": sysconfig.get_path("stdlib"),
+        "scheme": get_scheme(),
+        "virtualenv": get_virtualenv(),
+        "platform": get_operating_system_and_architecture(),
+    }
+    print(json.dumps(interpreter_info))
+
+
+if __name__ == "__main__":
+    main()
diff --git a/crates/uv-interpreter/src/interpreter.rs b/crates/uv-interpreter/src/interpreter.rs
index 660ec190e..aa167fc9a 100644
--- a/crates/uv-interpreter/src/interpreter.rs
+++ b/crates/uv-interpreter/src/interpreter.rs
@@ -15,7 +15,7 @@ use platform_tags::Platform;
 use platform_tags::{Tags, TagsError};
 use pypi_types::Scheme;
 use uv_cache::{Cache, CacheBucket, CachedByTimestamp, Freshness, Timestamp};
-use uv_fs::{write_atomic_sync, Simplified};
+use uv_fs::{write_atomic_sync, PythonExt, Simplified};
 
 use crate::Error;
 use crate::Virtualenv;
@@ -369,11 +369,17 @@ impl InterpreterInfo {
         let tempdir = tempfile::tempdir_in(cache.root())?;
         Self::setup_python_query_files(tempdir.path())?;
 
+        // Sanitize the path by (1) running under isolated mode (`-I`) to ignore any site packages
+        // modifications, and then (2) adding the path containing our query script to the front of
+        // `sys.path` so that we can import it.
+        let script = format!(
+            r#"import sys; sys.path = ["{}"] + sys.path; from python.get_interpreter_info import main; main()"#,
+            tempdir.path().escape_for_python()
+        );
         let output = Command::new(interpreter)
-            .arg("-m")
-            .arg("python.get_interpreter_info")
-            .env("PYTHONPATH", tempdir.path())
-            .env("PYTHONSAFEPATH", "1")
+            .arg("-I")
+            .arg("-c")
+            .arg(script)
             .output()
             .map_err(|err| Error::PythonSubcommandLaunch {
                 interpreter: interpreter.to_path_buf(),