I followed this guide to define a custom python interpreter (my system default python), so I edited /Users/amasson/Library/Application Support/org.inkscape.Inkscape/config/inkscape/preferences.xml with the foollowing:

But when I start inkscape, the file gets overwritten and the python-interpreter="/Library/Frameworks/Python.framework/Versions/3.12/bin/python3" part is removed.

Thus my extension (inkscape-silhouette) does not work.

What can I do to set the python interpreter?

I'm presuming that all instances of Inkscape were closed when you edited preferences.xml ? 

I tried it myself. 

I added my venv path:

python-interpreter="/home/name/.config/inkscape/inkvenv/bin/python3.10"

I then opened and closed Inkscape.

The line I had added was still there, but it had been moved several lines down in between some extension id entries.

I just tried and realized that the line python-interpreter="/path/to/python" is removed when I quite Inkscape so I changed the file once Inkscape is fully quit, and it works. Thanks!