I have done this as well (with Nix rather than Guix, but it doesn't matter). You do run into some friction sometimes, e.g. the UI themes from your main distro n

I have done this as well (with Nix rather than Guix, but it doesn't matter). You do run into some friction sometimes, e.g. the UI themes from your main distro not applying properly (because paths are all wrong). It does basically work, but it can be a bit jarring, depending on exactly what you're trying to do.