This is a good way to achieve what @Shamino outlined with mdutil. it’s easier as there are no commands to remember, and it does both things in that single step: excludes the drive from Spotlight’s indexing and deletes the existing index database.
I’m not sure if this excludes the volume from indexing or if it just excludes its content from search results.
It excludes the volume from indexing. Note that you can exclude folders as well, not just entire volumes.
The Search Privacy dialogue says “Prevent Spotlight from searching these locations.” (not “exclude these locations from search results”). And Apple’s support article on rebuilding the Spotlight index explicitly states, “To rebuild the Spotlight index for a disk or folder, turn Spotlight indexing off and back on for that item.” and then goes on to describe the procedure for adding items to the Search Privacy section of Spotlight in System Settings.
Rebuild the Spotlight index on your Mac – Apple Support (UK)
One does not hav to restart; a simple log out and log in is enough.
