Talking on his Absolute Radio podcast, Skinner quipped that hosts Ant and Dec "represent pure evil" for their role in the show.
Skinner said: "I don't think any of us for one moment thought it would be the glimpse through the gates of hell that the programme has turned out to be.
"I think it's quite significant the colours red and black are the colours of the devil, and indeed Nazi Germany."
Skinner continued: "I'll tell you what Simon Cowell has done, he's looked at the success of The X Factor and Britain's Got Talent, and he thought, 'Do we need the talent part of this? Can't we just have like 50/50 guessing?'."
He added: "It's made me feel very differently about Ant and Dec... to me now they represent pure evil.
"I'm now starting to think that Ant could be short for Anti-Christ, and Dec may be December, you know, the end of days, the dark times. I do, I think they're presiding over the death of British society."
Skinner joked of the participants: "They have been embraced by Lucifer, the souls of the contestants belong to Ant and Dec.
"I honestly think that this is a filthy, vile virus at the centre of British society that'll bring us all down. I think Ant and Dec should be hung up like Mussolini and Peretta Petucci."
Red or Black? struggled in the ratings during its first run on ITV1, but ITV chief executive Adam Crozier has said that it could be given a second series.
"There are some things we would do differently - ways you could change the programme," he said. "But there are long-term brands you have to invest in."
You can catch Frank Skinner every Saturday morning from 8am on Absolute Radio
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Watch Darren Thompson win £1 million during the first series of Red or Black? below: