I am a lefty. Grew up with right handed rifles and such. Served in the Army and had right handed M14 and m16. Not a problem.
Everything I have now including AR15 and AR10 type weapons are right handed except a Remington 870 which is lefthanded and just happened to be on sale at a local gun shop a few years ago.
I have a little more discomfort with revolvers but have adapted to loading and unloading.
I am currently looking for a semi auto handgun and it seems that most of them are totally right handed as far as a few items like safety and mag release and such. I am doing research on a couple of semi's in .40 cal that are ambidextrous.