The funnyman - who has written a new book, Revolution, about how he want to see society change - said he was “absolutely not” planning to succeed Boris Johnson.
In an interview to be broadcast on the XFM breakfast show today, Brand told presenter Jon Holmes: “I think we’ve already got a comedian who’s more known for his hair than his policies.”
Holmes asked him: “So this is a no, you’re not going to do it?”
Brand replied: “Absolutely not. We’ve already got a comic in the job. If you want a daft comedian running London, just leave things as they are. What I’m interested in is real change.”
At the weekend Brand’s representatives would not comment on suggestions that he could mount a challenge.
Discussing Mr Johnson in the interview, Brand said: “You can see why people like him. He’s a funny bloke, he’s affable, he’s got a nice way with him. But this is a time where a lot of Londoners are facing real fear about their homes.
“Boris Johnson, the elected mayor - elected to look after us, the people of London - takes five times more meetings with bankers than he does with civil servants, or representatives of the fire brigade, or any ordinary Londoner.”
Responding at the weekend to the possibility of the comic standing against him in 2016, Mr Johnson said: “Russell Brand may be about as convincing as a political theorist as a toaster made by Russell Hobbs, but he is at least engaging his left-wing audience with something they can recognise as passion.
“As a phenomenon he is a sign of the disintegration of the left and the weakness of Ed Miliband, and he therefore needs every possible encouragement,” he added in a column in the Daily Telegraph.
The interview will be broadcast on XFM from 8am and comes after Mr Johnson described Brand as a “nice chap” in his Daily Telegraph column.
The mayor said he would be “thrilled” if the comedian chose to run in 2016 as it would show that Ed Miliband had failed to enthuse the political left.
“Russell Brand may be about as convincing as a political theorist as a toaster made by Russell Hobbs, but he is at least engaging his left-wing audience with something they can recognise as passion,” Mr Johnson wrote.