"I do not call it betrayal but a huge mistake in management", Iranian state TV quoted Khamenei as saying, in his first reaction to the reimposition of U.S. sanctions.
There has been widespread speculation over whether Iran would be forced back to the negotiating table following Washington's withdrawal from the 2015 nuclear deal and reimposition of sanctions.
Fearing further economic hardship, thousands of Iranians in recent weeks have protested against the slump in the rial, sharp rises in the prices of some food items and state corruption.
"With better management and planning we can resist the sanctions and overcome them", Khamenei said. He says "along with sanctions, Americans have recently raised two more options, war and talks".
The rial has lost about half of its value since April in anticipation of the renewed United States sanctions, driven mainly by heavy demand for dollars among ordinary Iranians trying to protect their savings.
"Today's livelihood problems do not emerge from outside, they are internal", Ayatollah Khamenei said in another tweet.
State broadcaster IRIB said the new Fateh Mobin missile had "successfully passed its tests" and could strike targets on land and sea.
Khamenei referred specifically to the collapse in the currency, which has seen half its value wiped since early April. "We have never started a war and they will not confront Iran militarily", he siad.
A fortnight ago, Guards commander Mohammad Ali Jafari told Mr. Rouhani to take "revolutionary actions to control prices and prevent the enormous increase in the price of foreign currency and gold", in an open letter published by the conservative Tasnim news agency. "I do not call it betrayal but a huge mistake in management", Khamenei was quoted as saying. "Negotiation with the bullying and very eager government of the USA means giving it an instrument through which it can add to its hostility", he said.