The happy couple will soon be sending Joaquin, 17, to a university to follow in his siblings' footsteps, as Lola, 19, attends NYU and Michael, 23, graduated from New York University's Tisch School of the Arts in May.
"We had our kids so young -- we'd only been married for one year when we had Michael, so we have had kids pretty much our entire marriage," Kelly, 49, explained to People. "So when it comes to an empty nest, we're looking forward to it, honestly."
Mark added that one of the couple's famous friends waxed on about the advantages of having the house free of children.
"Rob Lowe says that once your kids leave, you pretty much never put clothes on ever again -- you're just naked all the time. So there's that too!"
Kelly then went on to say her children will still visit, giving the family of five "plenty of times together ahead."
"We love each other," she continued. "But we also really like each other, and we respect each other."
"I don't think any amount of college or growing up will take that away from us."
Meanwhile, Kelly said she was blessed to have her children around her when news broke of the death of her former "Live" co-host, Regis Philbin, in July.
"What I love to remember about him was his relationship with my kids," she said. "He would talk to kids like they were adults, he didn't care if they were 2 or they were 4. My kids responded to that in a way that was so, they just worshipped him."