"Melania Trump has emerged from hiding -- she hasn't been seen much since Winter Stormy Daniels hit D.C.,” Kimmel, the host of "Live," said during his monologue.
The first lady hasn't been seen in public too often lately, but she announced that she plans to meet with officials from Twitter, Facebook, Google and others as part of her fight against online bullying.
"Melania Trump holding a summit to stop cyberbullying is like Camille Cosby calling a meeting with Benadryl because 'it's making people woozy,'" Kimmel joked, referring to Bill Cosby's wife.
After mentioning Melania Trump's meeting with tech giants, Kimmel said, "Apparently the word 'irony' doesn't translate from Slovenian."
"All she has to do to fight cyberbullying is take a hammer to her husband's thumbs and phone," he added.
An administration official confirmed to ABC News on Tuesday that the first lady had invited tech executives to the White House to discuss online bullying and internet safety, but it is not clear if she plans to propose any policy changes.
Asked about the upcoming event, the first lady's spokesperson, Stephanie Grisham, said: "Mrs. Trump has simply asked for a meeting to discuss one of the many things that impacts children -- as she has done many times in the past, on several different topics."