“Now, the Americans, once again, have dispatched their agent as a saleswoman to the Gulf to spread lies,” state TV quoted Khamenei as saying at a meeting with visitors from the northwestern city of Tabriz.
Khamenei also accused the US of war-mongering and of turning the region into an "arms depot,” hitting back at US accusations that Tehran was moving toward a military dictatorship.
Khamenei didn't mention Clinton by name but he was referring to her tour of the region.
"But no one believes these lies because they know that America is the real war-mongering state. They have turned the Gulf into an arms depot," Khamenei said.
"They invaded Afghanistan and Iraq and are now accusing the Islamic Republic. Everybody knows that the Islamic Republic is for peace and brotherhood among all Islamic states in the world," Khamenei said, state television reported.
The comments by Khamenei were the latest sign of growing tensions between Tehran and Washington, which are embroiled in a long-running and escalating row over Iranian nuclear work the West suspects is aimed at making bombs.
Clinton on Tuesday wrapped up a visit to the Gulf during which she drummed up support for new round of UN sanctions against Tehran for pressing ahead with its sensitive uranium enrichment program in defianse of repeated Security Council ultimatums.
During her trip, Clinton said that Iran was moving toward a "military dictatorship" and that there was no "evidence" to support Tehran's claim that its nuclear program was entirely peaceful.
Clinton's tour of Qatar and Saudi Arabia aimed to isolate Iran from its Arab neighbors and to put pressure on Tehran's ally Beijing to drop its resistance to UN sanctions targeting mainly Iran's Revolutionary Guards.
Last week, Iran began enriching uranium to 20 percent purity, which Washington and other world powers say adds to evidence it is seeking a nuclear weapon.
Tehran denies the charge, insisting its goal is peaceful nuclear energy and research.
On Tuesday, President Mahmoud Ahmadinejad adopted a twin-track approach warning world powers against imposing sanctions but suggesting that Iran could suspend its enrichment of uranium to 20 percent purity.
"If anybody seeks to create problems for Iran, our response will not be like before. Something in response will be done which will make them (the world powers) regret" their move, Ahmadinejad told a Tehran news conference.
Ahmadinejad also said Iran could suspend enriching uranium to 20 percent if world powers supply it with the fuel required for a Tehran medical research reactor.
Khamenei said the Iranian people had punched its enemies "in the mouth" by turning out in large numbers to rallies last week marking the 31st anniversary of the 1979 revolution.
On Thursday, Iranian state television said "tens of millions of people" rallied to support the revolution across the country of 70 million, which is facing its worst domestic crisis in three decades after a disputed presidential election last June.
An opposition website said security forces fired teargas at opposition supporters staging a Tehran counter-rally on the Feb. 11 anniversary of the revolution that toppled the shah.
Khamenei, who like other Iranian leaders accused the West of stoking post-election unrest and meddling in Iran's internal affairs, accused "arrogant powers" of opposing the Islamic Republic because of its call for justice in the world. "We should mourn the day when the global imperialism praises us," he said.
