The first comments by 86-year-old Ayatollah Ali Khamenei come as violence surrounding the demonstrations sparked by Iran's ailing economy has killed at least 10 people.
The protests show no sign of stopping and follow US President Donald Trump warning Iran on Friday that if Tehran "violently kills peaceful protesters", the United States "will come to their rescue".
While it remains unclear how and if Trump will intervene, his comments sparked an immediate, angry response, with officials within the theocracy threatening to target American troops in the Mideast.
They also take on new importance after Trump said on Saturday that the US military captured Venezuelan President Nicolas Maduro, a longtime ally of Tehran.
The protests have become the biggest in Iran since 2022, when the death of 22-year-old Mahsa Amini in police custody triggered nationwide demonstrations.
However, the protests have yet to be as widespread and intense as those surrounding the death of Amini, who was detained over not wearing her hijab, or headscarf, to the liking of authorities.
Speaking to an audience in Tehran, state television aired remarks by Khamenei that sought to separate the concerns of protesting Iranians upset about the rial's collapse to "rioters".
"We talk to protesters, the officials must talk to them," Khamenei said on Saturday.
"But there is no benefit to talking to rioters. Rioters must be put in their place."
He also reiterated a claim constantly made by officials in Iran, that foreign powers such as Israel or the United States were pushing the protests, without offering any evidence.
He also blamed "the enemy" for Iran's collapsing rial.
Two deaths overnight into Saturday involved a new level of violence.
In Qom, home to the country's major Shiite seminaries, a grenade exploded, killing a man there, the state-owned IRAN newspaper reported.
It quoted security officials alleging the man was carrying the grenade to attack people in the city, some 130km south of the capital, Tehran.
The second death happened in the town of Harsin, some 370km southwest of Tehran.
There, the newspaper said, a member of the Basij, the volunteer arm of Iran's paramilitary Revolutionary Guard, died in a gun and knife attack in the town in Kermanshah province.
Demonstrations had reached more than 100 locations in 22 of Iran's 31 provinces, the US-based Human Rights Activists News Agency reported.
Iran's civilian government under reformist President Masoud Pezeshkian has been trying to signal it wants to negotiate with protesters.
However, Pezeshkian has acknowledged there is not much he can do as Iran's rial has rapidly depreciated, which sparked the initial protests.
The protests, taking root in economic issues, have heard demonstrators chant against Iran's theocracy as well.
Tehran has had little luck in propping up its economy in the months since its June war with Israel in which the US also bombed Iranian nuclear sites in Iran.
