Clinton, who has spent two decades in the national spotlight and narrowly lost her own bid to be president in 2008, said she enjoyed her job as the top US diplomat but found it physically grueling.
Asked by talk-show host Tavis Smiley if she would serve eight years, she replied: "No, I really can't."
"The whole eight -- that would be very challenging," she said in the interview broadcast Wednesday on public television.
"It's a 24-7 job and I think at some point, I will be very happy to pass it on to someone else," Clinton said.
Clinton repeated that she would not run again for president, saying she wanted a private life after a career in which she has served as first lady and a US senator.
"There are so many things I'm interested in, really going back to private life and spending time reading and writing and maybe teaching. Maybe some personal travel -- not the kind of travel where you bring a couple of hundred people with you," she said.
Clinton said she also hoped throughout her life to be a strong advocate for the rights of women and girls.
Clinton, who has often faced critical media coverage, said that she found it "a joy" to work with reporters covering the State Department.
"They are very substantive. They live and breathe the difficult issues that we cope with every day," she said.
She said she learned long ago to take press coverage "seriously but not personally" -- but acknowledged her concerns during her campaign to be the first female president.
"What I was not prepared for was a lot of the criticism that I thought had less to do with me and more to do with attitudes about women," she said.
"That was surprising to me -- it was 2007 and 2008. But that's something we still have to work on in this country."
Secretaries of state in recent times have rarely served more than one presidential term, although George Shultz was in office for six and a half years under Ronald Reagan.