The Bridesmaids star said she was "incredibly flattered" by the honour of being the cover star for the annual edition.
"I felt like it was saying something really lovely to my younger self, to my 20-year-old self," McCarthy told the publication of saying "yes" to it.
Watch the video above.
The Gilmore Girls star's selection was revealed on Tuesday by the US tabloid, as they previewed the cover for the issue which hits news stands on Friday.
McCarthy, 52, recounted for the magazine her upbringing on a farm in rural Illinois and how she went through a punk phase, complete with a mohawk and blue hair, when she was in high school.
"I was fascinated because when I walked down the street and I looked like that, it was the first time that I'd ever had people kind of make fun of me or say really mean things to me, even adults," she said.
"I just kept thinking, you don't know me, I didn't do anything to you. It was a real big eye-opener that people are just judging left and right."
McCarthy says it wasn't until her 30s, when she met husband and producing partner Ben Falcone, that she started feeling comfortable with herself.
The couple, who have two teenage daughters together, have been married since 2005.
The actor said she wants others to find similar peace of mind.
"When someone's being their authentic self and it hurts no one else in the world... The simplest rule is just be kind," she says.
McCarthy stars as the sea witch Ursula in Disney's upcoming live action The Little Mermaid, which will be released in May.
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