From Los Angeles, De Vito talked to Early Show Co-Anchor Jane Clayson about his role.
"It was surprising, wasn't it? I played a nice guy," says De Vito.
Yet, the movie is another dark comedy for the actor.
"I thought it was well written - zany, crazy characters," De Vito says. "When I heard it was a chance for Bette Midler and I to work together again - this is our third movie together - and I thought it was really good. I did Ruthless People, with her, and I tried to kill her in that movie. In Drowning Mona, she's already dead."
They also appeared together in Get Shorty, which he produced.
"I said, 'Bette, we had such a good time on Ruthless People together. I'm going to do this movie, Get Shorty. I'm acting in it, and I'm producing it; I want you to do a little scene,'" De Vito recalls.
"'The scene is not with me; it's with Gene Hackman,'" he continues. "And she said, 'Better.'"
Out of the three films, they have only been in two scenes together.
"We like being on the set together. We have not gotten to the point where we want to be in scenes together. We like hanging out behind the cameras," he quips.
His production company, Jersey Films, produced Getting Shorty as well as other successful popular movies, such as Pulp Fiction and Out of Sight, along with the new Julia Roberts film, Erin Brockovich, coming out March 17.
Last fall, TV Guide said De Vito's character on Taxi, Louie, was the most popular television character ever. "I was really honored," he says.
He was a favorite character "because he was so ruthless and so mean to everybody. I guess that's the way you get ahead," De Vito jokes.
"No, no. You know, people just dug it," he adds. "I was flattered and honored to be with some of my favorites, Lucille Ball, Jackie Gleason and Art Carney, and all the other people in television history," he reveals.
De Vito is preparing to send his oldest daughter off to college next year.
"The great thing about kids is that you know that when you have children, they're going to leave you," he says. "And if you do your job right, your job is to get them ready to leave you. So it's kind of ironic. It's a heartstring thing. It tugs really hard at you. But you really feel terrific that they're, you know, stable."
"My life is pretty much around my kids and my work. And we have a TV show that we just - we're going to do a pilot for. It's called Further Adventures. It's for CBS. Rhea Perlman igoing to be it in. She was on Cheers, remember her?" he says, referring to his wife.