"Those who have turned the Persian Gulf into an arms depot in order to milk regional countries for money have now dispatched their official to go around the Persian Gulf and spread lies against Iran," Khamenei said, referring to Clinton at a meeting with visitors from the northwestern city of Tabriz.
Khamenei said recent moves by Washington officials were "suicidal" for the United States, state television reported.
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 programme in defiance of repeated Security Council ultimatums.
During her trip, Clinton said that Iran was moving towards a "military dictatorship" and that there was no "evidence" to support Tehran's claim that its nuclear programme was entirely peaceful.
Clinton's tour of Qatar and Saudi Arabia aimed to isolate Iran from its Arab neighbours 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.
"We are not insisting on doing this (20 percent enrichment) although we have the capability. If they supplied the (uranium enriched to) 20 percent, the situation may change," he said, when asked if Iran would stop the controversial enrichment started on February 9.
Iran and world powers are deadlocked over a UN-drafted deal which aims to ship out Tehran's low-enriched uranium abroad for refinement by France and Russia to 20 percent purity and return as fuel for the Tehran reactor.
Iran insists the exchange of uranium must be simultaneous and carried out on its own soil. Western governments are strongly opposed to the demand.
