In Parental Guidance, Billy plays Artie, a grumpy baseball fan who's married to Diane, played by Hollywood legend Bette.
"Bette and I have known each other for a long time but we've never worked with each other, which everyone seems to think is odd," he said. "I kinda think that's good because it seems like a natural combination."
He recalled setting up a dinner meeting to discuss the film - "it was like we were married," Crystal said, laughing. "She ate off my plate, she wouldn't let me order, she drove me home, it just felt really comfortable."
He attributed this to a shared sense of "old showbusiness", adding: "We both have a respect for the performers we grew up with. It's an old form of showbusiness that unfortunately doesn't exist any more, and in that way we're throwbacks in the best way.
"There was a great patience with each other. I knew I trusted her and she trusted me. It ended up with a great deal of affection and respect, which is what a marriage has to be anyway."
The script originated from Billy and his wife Janice's own experiences looking after their grandchildren. Billy recalled: "It was great but exhausting and on the seventh day I rested, then came into the office and went, 'OK, here is the movie'."
Given he's hailed as one of the funniest men on the planet, you'd think Crystal would be a blast as a granddad.
"I can be conservative when I have to be, almost to a fault," he said. "That's how my dad was with me and it's sort of what you know. But the more I'm around them [the grandkids], the more you find you can be that conservative guy in a certain way that's more palatable."
:: Parental Guidance is released in cinemas on December 26.