The Odd Mom Out creator and star told fans Sunday at a Tribeca Film Festival screening that that she and Barrymore are "sisters forever."
Kargman's brother, Will Kopelman, and Barrymore publicly confirmed they were ending their marriage of almost four years in early April.
"Sadly our family is separating legally, although we do not feel this takes away from us being a family," they said in a statement at the time.
Barrymore guest stars on Kargman's Bravo show, playing the next-door neighbor to Kargman's character, Jill Weber.
And did Barrymore, a relative newcomer to Park Avenue, play an Upper East Sider with ease?
"[Barrymore] was a really good guest star. Wonderful. It was fabulous," Kargman told PEOPLE. "She lives on the Upper East Side, so she lives it. She's doing it. Her daughters are in the school that my kids went to. She's in it, and it's with a wink and a smile. And she did a beautiful job."
Drew Barrymore Shares Her Favorite Childhood Memories
Jill and Will's parents, Arie and Coco Kopelman; Jill's husband, Harry; and her young daughter Ivy also attended the event.
Kargman also revealed that she recently penned a book about the Kopelman family – and she says her clan has a dark sense of humor.
"I'd call my mom and she'd say, 'I can't talk we're Pinteresting tombstones,' " she explained to the audience. "It's about my family, these people right here, my parents, Arie and Coco. The whole time we were little kids, I would fight with my brother [Will] and [my dad would say], 'When mom and I kick the bucket and are pushing daisies, you've got to look out for each other.' "
She continued, "And every business trip. [My dad] would take the Concorde, and he would say, one of these days, that thing is going to blow. And I’d be in tears." She claimed that the dark sensibility made for a family that just "enjoys everything a little bit more."