“I am very flattered,” the star said of the title.
Roberts first earned the cover at age 23 in 1991 and has since been given the honor in 2000, 2005 and 2010. Her five covers put her marginally ahead of friend George Clooney, who has been named People's "Sexiest Man Alive" twice.
“I’m going to mention that in my Christmas card to the Clooneys this year," Roberts joked.
When Roberts covered the issue the first time, her iconic film, Pretty Woman, had just been released, and the 49-year-old admitted she didn't quite realize just how big the film was when it came out.
"People say, 'Oh, when Pretty Woman came out it must have really changed your life,' and it's kind of become this joke, but the truth is I was out of town when Pretty Woman came out," she said. "I was in another movie in this tiny little town that was showing Star Wars in its first run. I remember reading...'Pretty Woman came out this weekend and made this much money' and I thought, 'Is that a lot of money? Is that good? Is that great?' I didn't really know."
The actress also opened up about life with husband Danny Moder, and their children, twins Hazel and Phinnaeus, 12, and son Henry, 9, telling the magazine, "I think I'm currently peaking."
Twenty-six years after her first cover, Roberts revealed that she hopes the next 26 years of her life bring happiness for her family.
"Seventy-five," she laughed. "If I can just grow gracefully-ish old and watch my kids grow up and realize their dreams, and find their person in life, and hopefully have a family and little creatures for Danny and I to spoil, that's what the winter of life is supposed to be about."
Roberts will cover the magazine's May 1 issue with the title, and other featured stars include Viola Davis, Taraji P. Henson, Chrissy Metz, Mandy Moore, Emma Watson, Oprah Winfrey and Carrie Underwood, E! News shares.
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