The actor told ITV's Daybreak that the BBC sci-fi drama should "give [a female lead] a whirl".
Barrowman, who played Jack Harkness on 'Doctor Who' and its spinoff 'Torchwood', said: "We've had great guys playing the role.
"The character of River Song (Alex Kingston) was so popular in the last part of the series and it [had] such an impact - why shouldn't we have a female Doctor?"
He added: "If it doesn't work, she can always regenerate back to a man."
Various female names have been put forward for the iconic role, which celebrates its 50th anniversary this year.
She told Radio Times: "My brother sent me a text saying, 'Congratulations, they've released odds on you being the new Doctor Who' - which we thought was very funny.
"No-one's ever asked me about it. I assume they would have to ask me for it to be true."
And Helen Mirren recently called for a female to land the role, after she was also linked to the part.
Denying rumours she was set for the Tardis, she told 'Daybreak' earlier this month: "I’m not going to be the first female Doctor Who, no, no, no, absolutely not, I absolutely wouldn’t contemplate that.
"But I do think it’s well over-time to have a female Doctor Who. I think a gay, black female Doctor Who would be the best of all."
The BBC is expected to announce the identity of the actor or actress replacing Smith in August or September.
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