In a televised address marking the start of Eid al-Fitr, the festival that follows the Muslim holy month of Ramadan, Khamenei said the agreement signed Tuesday on the nuclear issue would not affect Iran's stance on other regional or bilateral matters.
"Our policies toward the arrogant government of the United States will not be changed at all," he said.
Khamenei said the negotiations with the United States and other world powers on Tehran's nuclear program were an exception because they served Iran's national interest.
Bilateral issues currently at stake between Washington and Tehran include the fate of three Americans of Iranian background who are currently detained in Iran, as well as the status of a fourth American, who was a CIA contractor and remains missing after visiting the country.
Their families have questioned how a deal could have been made
on the nuclear issue without addressing their cases.
U.S. President Barack Obama has strongly defended the landmark deal, which was the result of 20 months of talks, telling reporters Wednesday
: "This deal is our best means of ensuring Iran does not get a nuclear weapon."
His real audience, however, was skeptical Democrats
on Capitol Hill, who could join with Republicans to scuttle the complex agreement brokered in Vienna
In a bid to bolster support, White House officials have been trumpeting the measure for the limits placed on uranium enrichment and broad access for international inspectors.
Obama also noted that he has met with families of some of the Americans held in Iranian custody, and said his administration was "working diligently to try to get them out."
The nuclear deal must also clear certain hurdles in Iran before it comes into force.
Khamenei said the draft agreement would have to be ratified through the legal process in order to be accepted in Iran. "There is predetermined legal course that this agreement must go through, and it will go through, God willing," he said.
He called on the Iranian officials who would be engaged in the approval process to put the interests of Iran and its people first.
Under the agreement reached in Vienna, sanctions that have choked the Iranian economy will be rolled back in return for restrictions on its nuclear activities, which will be inspected by the International Atomic Energy Agency.
Iran insists its intentions are peaceful.
But Israeli Prime Minister Benjamin Netanyahu described the deal as "a stunning, historic mistake," which would help Iran obtain nuclear weapons capability.