Rouhani was met by protesters chanting "Death to America," in response to his historic, 15-minute phone call with U.S. President Barack Obama, the first top-level conversation of its kind in 30 years, held just before the Iranian leader left for the airport Friday.
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Opponents to the breakthrough conversation are angry at the prospect of a detente between Tehran and Washington, which they see as contrary to the principles of the Islamic Revolution.
Protesters pelted the presidential motorcade with eggs and tried to block it, according to media reports.
The semi-official Mehr news agency reported at least one demonstrator hurled his shoes in Rouhani's direction, a gesture considered an insult in the Arab world.
When Rouhani was elected in June, he said he wanted to reach a deal over the nuclear issue in three to six months.
He has also asserted that Iran does not seek to create a nuclear bomb, as Western powers have long suspected.
On his return to Tehran, Rouhani said the conversation with Obama centred on nuclear issues.
"I said in the telephone conversation that the nuclear program is not only a right of the Iranian nation and a matter of [technical] development, but also, and more importantly, it is a matter of national pride for the Iranian people. [Obama] approved the right of the Iranian people to nuclear energy."
Possibly standing in Rouhani's way of his overtures to the U.S. is an array of hardliners, led by the hugely powerful Revolutionary Guard.
However, Rouhani supporters greeted him with placards thanking him for seeking peace instead of confrontation. One banner read: "Yes to peace, no to war."