"I don't want to waste my time on answering the rants and whoppers of the brute US president," Khamenei said in a speech to students in Tehran, published on his Telegram channel.
It was his first response to Trump's bellicose speech last Friday in which he called for tougher sanctions to curb Iran's "destabilising activities" in the Middle East.
"They are angry as today the Islamic republic of Iran has disrupted their plans in Lebanon, Syria and Iraq," Khamenei said.