Her latest role, however, is taking her in a very different - and very dramatic - direction.
"Tuesday" deals with death, and Louis-Dreyfus plays a mother trying to come to grips with the fact her daughter, Tuesday, is dying.
When death comes to get the teenager, in the form a talking bird, we see pain, love and loss as two people meet the moment together of having to say goodbye.
"It required a kind of deep dive into areas that aren't very comfortable," said Louis-Dreyfus. "This film explores themes of obvious grief and loss and denial, and also explores the ferocity of the parent-child bond, in both directions."
Lola Petticrew plays the teenager in a movie that's both dramatic and unexpected - a fairy tale of sorts but with that happily ever after in question.
"I think everybody always wants to be surprised. There's something about being surprised that absolutely tickles everybody pink," said Petticrew. "Go book that cinema ticket and sit in a theater with a bunch of other people and experience a communal catharsis."
Louis-Dreyfus said the script itself was pretty unusual.
"I mean, really, the script is a work of art in my view, and the fact that it was a dramatic role made it all the more juicy, from my point of view, because it was an opportunity to, you know, try something that people hadn't seen me do before."
"Tuesday" is playing in theaters now.