The Hollywood star previously launched an outspoken defence of Meghan, comparing her treatment with that of Diana, Princess of Wales.
Now he has explained why he wanted to speak up for “a really kind, smart and intelligent young woman”.
“I’ve seen it when the press can turn on you for sort of ridiculous reasons and for almost nothing and it seemed to me to be a little unjust since she hadn’t done anything except just happen to live her life,” the actor told ITV show Good Morning Britain.
Clooney, who is a friend of Harry and Meghan and attended their wedding with his wife Amal last year, said: “She’s a really kind and smart and intelligent young woman and they’re a really wonderful, loving couple. Most of it you can just shrug off and not pay attention to, but sometimes it’s unkind.”
Clooney’s intervention came amid reports of a rift between Meghan, who is pregnant, and her father Thomas Markle. The US actor had said history was repeating itself in the case of Meghan and Diana and warned: “We’ve seen how that ends.”
Speaking on television, he also joked about the royal family at a recent event at Buckingham Palace, quipping: “Charles got really crazy and started dancing on the tables ... I was surprised to see that.
“He had such good dance moves. Sir Tom Jones sang, which was fun. It was actually a really great night.”
Clooney was in Edinburgh on Thursday collecting a cheque for the Clooney Foundation for Justice, which is he and his wife’s charity. The glamorous couple attended the People’s Postcode Lottery Charity Gala at McEwan Hall.
The Hollywood star also said he was too old to play spy 007, saying: “I look like James Bond’s grandfather.”
But he backed Luther star Idris Elba to take over from Daniel Craig, saying: “I’ll say it 1,000 times – Idris Elba should be Bond, period. He’s elegant, he’s handsome, he’s very ... he should be Bond. I’m shocked that they haven’t just offered it to him right now.”
The father of young twins, Alexander and Ella, Clooney also spoke of his love of pranks.
“I was shooting a TV show in Italy, I went and I got a nappy and I put Nutella in it and I threw it in the trash can and then I came in an hour later,” he said.
“There was an Italian housekeeper in this place we were staying in ... I open up the trash can, I pull out the nappy with the Nutella and I opened it up and I sniffed it and I tasted it and she screamed and ran out of the room.”