"I don´t want to waste my time on answering the rants and whoppers of the brute U.S. president", Khamenei said in a speech to students in Tehran, published on his Telegram channel.
"Everyone be assured that this time, too, America will be slapped and defeated by the nation of Iran".
He said Iran would stick by its commitments under the 2015 nuclear deal, which Trump has threatened to "terminate" unless the US Congress tightens sanctions on the country.
The deal signed in Vienna in 2015 between Iran and six world powers - the U.S., Britain, Russia, France, China, and Germany - saw internationally observed limitations to Iran's nuclear weapons program in return for the lifting of worldwide sanctions. Pouyanne has said Total would withdraw from Iran if obliged by law.
Speaking in a Wednesday meeting with a group of elite students in Tehran, Ayatollah Khamenei strongly condemned Europe for reiterating the United States remarks about Iran's regional presence and missile program, saying that such issues are none of their business.
Tehran has repeatedly pledged to continue what it calls a defensive missile capability in defiance of Western criticism.
He also said that his new strategy begins with imposing tough sanctions on the IRGC, accusing Iran of "proliferation of missiles and weapons that threaten its neighbor's global trade and freedom of navigation".
Tehran has said it seeks only civilian nuclear energy from its enrichment of uranium, and that the program has nothing to do with missile development efforts.
"Why do YOU have missiles? We do not accept that Europe sings along with America's bullying and its unreasonable demands", Khamenei said.
It has called upon the Islamic Republic not to "undertake any activity related to ballistic missiles created to be capable of delivering nuclear weapons". Iran says it has no such plans.
Congress must now decide whether to reimpose some economic sanctions that were lifted as part of the nuclear deal in return for Iran limiting sensitive nuclear activities.