Her family said that she died from cancer that was "only recently discovered." Alley was 71.
"She was surrounded by her closest family and fought with great strength, leaving us with a certainty of her never-ending joy of living and whatever adventures lie ahead," her adult children, True and Lillie Parker, said in a statement. "As iconic as she was on screen, she was an even more amazing mother and grandmother."
Travolta, who along with Alley was one of the most prominent faces of Scientology, was quick to comment that "Kirstie was one of the most special relationships" he has had.
"I love you Kirstie," Travolta wrote. "I know we will see each other again."
Jamie Lee Curtis, who co-starred with Alley in the second season of Ryan Murphy's horror series Scream Queens in 2016, posted her own kind remembrance.
"She was a great comic foil in @tvscreamqueens and a beautiful mama bear in her very real life. She helped me buy onesies for my family that year for Christmas," Curtis recalled. "We agreed to disagree about some things but had a mutual respect and connection. Sad news."
Steve Guttenberg shared an anecdote from his time shooting the film It Takes Two with Alley, praising her "generosity" and "soulfulness."
There were many more, including Kristin Chenoweth, who appeared on Alley's post-Cheers TV Land sitcom Kirstie, and Ever Carradine, who credited the Alley-fronted sitcom Veronica's Closet with launching Carradine's career.