Markle, who shares the same name as their father, who Meghan is also estranged from, is taking part in Big Brother VIP, the Australian version of Celebrity Big Brother.
It was clear from the first trailer for the series that he intended to hold nothing back in his negative view of his half-sister as he labelled himself "the biggest brother of them all" and got stuck into criticising her.
The 55-year-old said: “I told Prince Harry, ‘I think she’s going to ruin your life.'
“She’s very shallow.”
Markle has moved into the Big Brother VIP house alongside 11 other contestants with a claim to fame, including Caitlyn Jenner.
He was not invited to the wedding of Meghan, 40, and Prince Harry, 36, and at the time reportedly wrote a scathing letter to Harry warning him off the marriage.
The letter is said to have told Harry it was “not too late” to turn back, that Meghan was “obviously not the right woman” for him, and that Suits star Meghan was acting “the part of a princess like a below C average Hollywood actress”.
Markle has previously antagonised his half-sister by taking part in a beer advert alongside a Meghan look-a-like where he pretended to burgle Buckingham Palace, eventually choosing a crate of beer over the Queen's crown.
He said at the time that he "didn't think anyone would be upset by it", even suggesting the royals might find it funny.
Meghan and Harry now live in the US with their two children Archie and Lilibet, and earlier this year gave a tell-all interview to Oprah Winfrey where they spoke out about their experience as royals.
The couple said a senior royal had questioned how dark Archie's skin would be before his birth, and also claimed Meghan had received little support over her mental health struggles.
Watch: Meghan Markle's half-brother calls her shallow