The comedian called on his studio audience to respect the two men, Timothy Phelps and Steve Drain, for bravely agreeing to appear on his show and then debated their beliefs that homosexuality is wrong in the eyes of God.
Drain accused Brand, who played a gay man in the movie musical Rock of Ages, of choosing a profession that makes "a mockery of sin" and then attacked members of his audience for sinning, while quoting text from The Bible to support their argument that homosexuality is wrong.
Brand asked the two church leaders, "Have you considered that The Bible, like all religious doctrine, may be allegorical and symbolic, to direct us toward one holy entity of love, as opposed to a simplistic, litiginous text to direct the behaviour of human beings?"
He then attempted to lighten the tense proceedings by playing a game he called Heaven & Hell with the religious extremists, during which they condemned famous people like Gandhi, Tom Hanks and Madonna to hell, before he brought out three gay pals.
As the Westboro Baptist Church representatives and the gay men exchanged un-pleasantries, Brand urged the group to respect each other, joking, "We're trying to conduct a telly programme," and then telling his pals, "Stop upsetting my mates, they're trying their best to be homophobic over here."
After the TV stand-off, which will air on an upcoming episode of Brand X, the comedian followed his guests offstage asking them to "give me a cuddle".