Famke JanssenFamke Janssen was originally cast as Serleena, and even completed some of the filming, but was forced to drop out of the project due to a death in the family. Lara Flynn BoyleLara Flynn Boyle was then cast in her place.
When Agent J first "kills" Serleena and after a quick cut, Serleena grows back and says, "Feed Me" referencing the musical Little Shop of Horrors.
The original pug from Men in Black was used to play Frank again, but since the pug was now seven years old, they used makeup to hide the gray fur around its nose.
When J and K go to the Worms' apartment, they are speaking to each other in Huttesse from the Star Wars films.