Alley's big break didn't come until she was 31 years old, when she was cast to play a Vulcan in Star Trek II: The Wrath of Kahn.
"The plan was to come to California and be an actress, but I didn't want to be a poor and starving actress, so that's why I went on game shows and I was an interior designer, but I didn't have any clients, because I didn't know anyone in California," Alley told ET. "I remember when I got Star Trek, I was in the middle of decorating houses."
While Alley told ET that she was "very grateful" for the job and "thrilled" to take it, it wasn't the gig she'd envisioned. "I sort of thought my first role would be, like, Body Heat. I didn't know I'd be playing a Vulcan," she said.
Alley's first comedic role came in 1987, when she played Mark Harmon's love interest in Summer School. "You mean the world's sexiest man," Alley joked to ET of her co-star. "Mark's a great guy."
Later that year came perhaps Alley's best known role of Rebecca Howe on Cheers.
"At first I thought, 'Do I want it?'" Alley said. "Not so much being Cheers, but 'Do I want to go to work five days a week?'"
It turned out to be a good thing that she accepted the job, as she earned an Emmy Award for her performance in 1991.
"It's a wonderful acknowledgment of the work that I've done," Alley told ET at the time, before joking, "More than that it means not losing."
Amid her successful Cheers run, Alley nabbed the leading role in Look Who's Talking, which she starred in opposite John Travolta. She joked to ET that "it was John" who charmed her into accepting the job.
"I didn't know job before I took the film. It's just really easy for us," she said of their natural chemistry. "I'd do another movie with him."
The pair reunited in 2013, when Travolta made an appearance on Alley's TV Land sitcom Kirstie. It was when ET was on the set of that episode that Alley revealed how far back her Travolta crush went.
"Here's the real truth. When I moved to Hollywood, I was going to marry John Travolta. Now, I'm sure I'm the only woman in the world who felt that way," she quipped. "When I met him at my agent's house, I was trying to hold it together a little bit. I wanted to go, 'Ahhh!'"
During ET's last interview with the actress at the 2019 premiere of Travolta's film The Fanatic, Alley gushed about her "chameleon" friend and weighed in on the possibility of a Look Who's Talking reboot.
"I'm going to try to convince him. As you know, he's his own man," she said, before joking, "He responds to money... and threats."
As for her own career, Alley served as a Jenny Craig spokesperson, starred in the Showtime sitcom Fat Actress, executive produced the reality show Kirstie Alley's Big Life, came in second on Dancing With the Stars, competed on The Masked Singer and more.
"I feel like I have the most blessed, wonderful, for real, fun life in the world... I am one of those people that didn't think I'd make it past 30. I thought I was going to go down with the rock stars at 28, so every year to me is a bit of a treat," she once told ET. "... I could see myself being 95 doing movies or shows, because I really love doing it."