Asked if he minded when people ask when he is "coming out", he told the magazine: "If I was living 200 years ago in a coal mine, maybe, but I work in possibly the gayest industry in the world! Music and TV!
"It would make no difference to my life or my career. A lot of my friends are gay, but I'm not and don't even think that way any more."
He added: "I couldn't care less (if people think I'm gay) because it's nothing to be ashamed of. It feels like such an antiquated question now."
Questioned on whether he picks women who he fancies to work on his shows, he laughed: "A lot of them, yes, I'm not going to lie."
Cowell said of former X Factor and US X Factor judge Cheryl Cole: "I think my entire production staff – including a lot of gay people – were in love with Cheryl.
"I mean, literally, when she walked on set on the first day in the UK I thought that she was one of the most beautiful women I have ever seen in my life."'
Cowell, who is about to return in Britain's Got Talent, said that he was "not actively looking for a wife".
"I'm happy single... I tend to be in a relationship more than being single. Terri (Seymour) lasted six years, Mezhgan (Hussainy) lasted two years, and that was in a nine-year block, so I was only single for about a year out of those nine years," he said.
Cowell, who said that he does "several hundred" push-ups a day, has Botox, and takes vitamin infusions, stated of his previous relationships: "I am a good breaker-upper."
He admitted that there are moments on his TV shows – often accused of being exploitative – which make him feel "uncomfortable".
But he denied that his shows exploit people. Asked whether he thought that he was playing with people's lives he said: "It happens on every show you make.
"There is a moment where you feel uncomfortable, but then you look at things with perspective and the truth is – over the years – the show has benefited a lot of people's lives who wouldn't have had an opportunity."
He said that contestants had to be "interesting" but said that viewers did not want to see troubled people on his shows.