The actor, who played Mike Delfino in Housewives, will appear in the TV Land show's season finale on May 16, TV Guide reports.
Denton will play a character known as Kerouac Cowboy, who becomes a love interest for Joy (Jane Leeves) after they connect over a CB radio.
The 49-year-old recently admitted that he was "really surprised" by his latest Desperate Housewives storyline, which has dominated the last few episodes airing in the US.
"Any other year, I would have been disappointed," he said of his plot for the final season. "But at this point I figured, well, we made it... As an actor, you just hope people care."
Kristin Chenoweth, Liza Minnelli and Ed Asner are among the other stars to have signed on for guest appearances in Hot In Cleveland.
The show airs Wednesdays at 10/9c on TV Land.