While the crowd was small - about 200, mostly students, gathered at the entrance to the Tehran Research Reactor - the event was the first such officially approved demonstration in months.
It coincided with the penultimate day of talks in Vienna between Iran and the United States and other world powers aimed at a permanent deal that seeks to block all routes to Tehran developing a bomb.
As a sign of defiance on Iran's nuclear activities, several protesters wore white lab coats in memory of four Iranian atomic scientists that Tehran says were assassinated by Israel and the United States.
"Nuclear energy is our absolute right," and "Sanctions won't stop us," read placards held by the protesters.
The crowd chanted "Death to America" while a speaker rounded on the conduct of the year-long negotiations which entered their final 36 hours with a deal hanging in the balance.
President Hassan Rouhani and Mohammad Javad Zarif, the foreign minister who is leading the Iranian side in the Austrian capital, "do not know how to do diplomacy", the speaker said.
The protest highlighted the feelings of some Iranians that the government has already made too many concessions on its nuclear programme during the discussions of the past year.
However, an Iranian source in Vienna signalled openness to extending the talks by six months or even another year.
Such an extension would be under terms of an interim deal reached in Geneva last November that traded a temporary freeze on some of Iran's nuclear activities for limited sanctions relief, the source said.
Such a deal is aimed at easing fears that Tehran could develop nuclear weapons under the guise of its civilian activities.
The Islamic republic denies it wants to build an atomic bomb and insists its nuclear programme is entirely peaceful.
