Last week one paper published a highly personal letter they said was written by Markle to her estranged father in which she begged him to "stop lying ... stop exploiting my relationship with my husband".
Speaking at an event in Los Angeles this week, Clooney, 57, claimed that history was repeating itself in the case of Meghan and Diana, warning: "we've seen how that ends".
Since Markle and Prince Harry began dating, the duchess has been subject to media scrutiny about everything from her "messy" bun to her troubled relationship with her father.
The letter in question, which Markle wrote to her father in 2018 after he continued giving interviews to the press and was first alluded to in an interview with alleged close friends of the Duchess in People, was made public over the weekend when Thomas Markle shared it with The Mail on Sunday.
They also expressed their concerns for Meghan and her unborn baby.
The letter's existence was revealed when five of Meghan's pals anonymously spoke out to defend pregnant Meghan, 37, saying she had tried reaching out to her dad but instead been met with a request to do a photo shoot together.
She later added: "He did try to contact her she was the one who ignored him and all of us".
During Harry and Meghan's tour of Australia, New Zealand, Fiji and Tonga, last fall, they unveiled six dedications to the QCC and welcomed commitment to the initiative by its latest member, Kiribati.
"So, numerous things in that letter were written with the public in mind".