Tranny leaking from small plug next to tailshaft

Will I have to drain the fluid first before I can use the permatex?

If you just want to seal it from the outside you will need to spray it well with carb or brake cleaner and alternate a couple of times with air if you can to get it dry of fluid so the Permatex will stick well.

I would also press the Permatex in with a finger to get it down in the gap as much as possible.
Then you can wipe off the extra and let it set up.
Should be fine after that.

No draining of any fluid needed, but you might want to run it in neutral for 30 seconds before you start on it to get the fluid level down to normal.
If you do it cold without a startup, the fluid level may be pretty high and just re wet the surfaces you want nice and oil free.