Patrick J. Adams, who played Meghan’s love interest in the US series, branded the Royal Family “obscene” for “promoting and amplifying accusations of bullying” against her.
The actor went on to accuse the royals of being “bankrupt of decency”.
After posting the Twitter thread on Friday evening, Piers weighed in, calling the US actor a “jumped-up little twerp”.
The Good Morning Britain presenter tweeted: “Actually, what’s ‘OBSCENE’ is your friend trashing her husband’s family on global TV as the Queen’s 99-yr-old husband lies in hospital. How dare you attack our Royal Family like this, you jumped-up little twerp.”
He added: “Meghan Markle’s showbiz mates who flew over and grovelled up to the Royals at her wedding now publicly trashing the Monarchy - and suggesting it be abolished. Disgusting.”
Following Patrick’s tweets, Suits creator Aaron Korsh also spoke out to share his support for Meghan, tweeting: “Meghan Markle is not a monster. She’s a strong woman with a kind heart who’s trying to make her way in an unimaginable situation.”
Watch: The key revelations from Meghan and Harry’s Oprah interview
In a lengthy Instagram post shared on Friday, Abigail Spencer, another former Suits co-star, also shared a tribute to Meghan.
Earlier this week, Piers attempted to question Harry’s friend Ben Fogle about his thoughts on the Duke and Duchess’s interview with Oprah Winfrey during an appearance on Good Morning Britain.
But Ben, who was there to discuss his new documentary about the Chernobyl nuclear disaster, quickly shut Piers down.
“To be honest, Piers, I don’t want to dodge your question, I think you’re overestimating my friendship with the protagonists you’re talking about,” Ben said.
“In the middle of the wilderness here [in Suffolk] I’ve tried to abstain from news, and I try to stay out of other people’s business. I think it’s a very valid time for everyone to have an opinion, but it’s not really for me to say.”
Ben’s interview on GMB came a day after Susanna Reid accused her co-host of being “obsessed” with Meghan, and having a “negative filter” when it came to the Sussexes.
And Susanna isn’t the only one to have accused Piers of being unfairly critical of Meghan.
She told him: “You are a man, privileged to have power and influence and you are using your platform so irresponsibly to spout out this personal vendetta with nasty and vile comments knowing fully well that your words are containing bigotry, misogyny, sexism and racism.
“You don’t take responsibility for how you have contributed to the so-called royal crisis.”
Watch: How Are People Reacting to the Harry and Meghan's Interview?
This article originally appeared on HuffPost UK and has been updated.