The actor, who has recently played a recurring role on Glee, told Ryan Seacrest's KIIS-FM radio show that while he is "flattered" by the suggestion, he ultimately has other plans for his career.
"I don't want to replace anyone, especially Charlie Sheen. It's just not where my head is at," he said.
"It's all been very flattering. But nobody has officially talked to me and, quite frankly, as flattering as it is, it's really not part of my career plan right now. I'm just on a different trajectory."
Stamos added that he doesn't believe Sheen can truly be replaced and wishes that disputes between the star and show executives would allow for his return to the CBS comedy.
"Charlie is great on that show and people love Charlie on that show and people love the way the show is," he explained.
"So, in the big scheme of things, apparently there's a lawsuit going on, so I don't know, but I hope it works out and I hope he goes back and people get the show that they love."