The royal couple, who are due to marry on 19 May at Windsor Castle, went to the heart of London's Caribbean community for their first official visit in the capital.
Widdecombe, a right-wing former Prisons Minister turned reality television contestant, made the remarks to fellow housemate Rachel Johnson and others, while having make-up applied by Made In Chelsea star Ashley James.
The 70-year-old said: “I think she's trouble.
“Background, attitude... I worry. I add it all up and I'm uneasy but there we go.”
Ms Markle had earlier chatted, joked and even hugged young presenters from a youth radio station the couple visited to learn more about the work of the not-for-profit broadcaster that trains the presenters, producers and station managers of tomorrow.
And Harry, the self confessed joker of the royal family, even exchanged an extravagant fist bump with one of the DJs, after a little coaching in how to perform the greeting.
Crowds had gathered outside the studios of Reprezent FM and they cheered and screamed when they were acknowledged by the couple who held hands when they first arrived, and later waited in freezing conditions after the 45 minute visit overran by almost half an hour.
After waving to the crowds the couple were whisked inside Pop Brixton, a community project that houses independent local businesses, start-ups, new restaurants and the not-for-profit station in shipping containers.
The mixed-race actress was thought to be making her first visit to Brixton which is traditionally considered the home of London's Caribbean community after some of the West Indian immigrants, who arrived on Empire Windrush in 1948, settled in the area.
The mood after the royal engagement was summed up by Jeremiah Asiamah, 20, who said: “They became family in the space of five minutes.
“She (is) beautiful, such an amazing character, if there's any way you could describe a power couple in this modern day and age, it's definitely them.”
Viewers of Celebrity Big Brother seemed unimpressed with Widdecombe's comments.
genheron wrote: “Ann Widdecombe says Meghan Markle is 'trouble'. Have you ever heard such shameless classism?”
JoeAndertweet wrote: “Of course Ann Widdecombe doesn't like Meghan Markle because of her 'background'.”
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