Obama was asked by the New Yorker magazine about the prospect of both Clinton and Joe Biden, the US Vice-President, running for president in 2016.
"I think that, for both Joe and for Hillary, they've already accomplished an awful lot in their lives. The question is, do they, at this phase in their lives, want to go through the pretty undignifying process of running all over again," Obama said.
Biden, who trails far behind Clinton in polls of potential Democrat candidates, has expressed interest in running but would be 74 if he won - the oldest president ever in the White House.
The New Yorker describes Obama as unable to "hide his bewilderment that his friends would want to subject themselves to another presidential campaign".
Clinton has said she will decide by the end of the year whether to run for president, citing the forthcoming birth of her first grandchild as one reason she has not yet officially made up her mind.
But her clear interest in a second bid has revived the market for right-wing books, often thinly sourced, claiming to offer prurient details of the Clintons' private lives. Such books, last popular during Bill Clinton's presidency, have been doing a roaring trade and Blood Feud, which claims to reveal a bitter relationship between the Obamas and the Clintons, is outselling Clinton's autobiography, Hard Choices.