Trump reiterated his threat that Iran would be bombed if it does not accept his offer for talks outlined in a letter sent to Iran's leadership in early March, giving Tehran a two-month window to make a decision.
"The enmity from the US and Israel has always been there. They threaten to attack us, which we don't think is very probable, but if they commit any mischief they will surely receive a strong reciprocal blow," Ayatollah Ali Khamenei said.
"And if they are thinking of causing sedition inside the country as in past years, the Iranian people themselves will deal with them," he added.
Iranian authorities blame the West for recent unrest including 2022-2023 protests over the death in custody of Mahsa Amini, a young woman detained for allegedly flouting hijab rules, and nationwide protests in 2019 over fuel price rises.
Iran responded to the US letter with President Masoud Pezeshkian explaining on Sunday that Tehran would not enter direct negotiations with Washington but was willing to continue talks indirectly as per an injunction from Khamenei.
"An open threat of 'bombing' by a head of state against Iran is a shocking affront to the very essence of international peace and security," Foreign Ministry spokesperson Esmaeil Baghaei tweeted.
"Violence breeds violence, peace begets peace. The US can choose the course and concede to consequences."
In his first 2017-21 term, Trump withdrew the US from a 2015 deal between Iran and world powers that placed strict limits on Tehran's disputed nuclear activities in exchange for sanctions relief. Trump also reimposed sweeping US sanctions.
Since then, Iran has far surpassed that deal's limits on uranium enrichment.
Western powers accuse Iran of having a clandestine agenda to develop nuclear weapons capability by enriching uranium to a high level of fissile purity, above what they say is justifiable for a civilian atomic energy program.
Tehran says its nuclear program is wholly for civilian energy purposes.
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