"Therefore, it is essential to entirely abandon hope in Europeans," he said in an address to the members of the assembly on Thursday, his website reported.
Following the United States' exit from the 2015 nuclear deal and its reimposition of sanctions against Tehran last year, Europeans expressed support for the agreement and vowed to take measures to protect Iran's interests.
According to Foreign Minister Mohammad Javad Zarif, Europe made 11 commitments to salvage the deal following the US departure, but none has been fulfilled and their steps have failed to address Iran's economic concerns after over a year, Financial Tribune reported.
"Europeans have not honored any of their commitments and this is the strongest reason why they must not be trusted in any affair," he said.
The Leader, however, noted that communication, visits and signing contracts with them are no problem, but they absolutely must not be trusted.
Flag of Hostility
European countries have also recently put in efforts to mediate between Iran and the US to defuse Middle East tensions.
"Europeans enter the scene apparently as mediators, they negotiate, contact, make calls, make lengthy speeches and make commitments, but they are all empty," the Leader emphasized.
The already volatile Middle East region saw a further escalation following the Sept. 14 attack on Saudi oil facilities, which Riyadh and Washington have blamed on Iran.
London, Berlin and Paris backed the US with regard to the accusation, urging Tehran to agree to new talks with world powers on its nuclear and missile programs and regional security issues.
They issued a joint statement after their top leaders met at the United Nations in New York on the sidelines of the annual gathering of world leaders.
"These few European countries openly show hostility to the Islamic Republic. Their motives for hostility with the Islamic Republic are not inherently different from those of the US," the Leader was quoted as saying by Khamenei.ir.
Ayatollah Khamenei noted that Iran has not closed the door on establishing relations and negotiating with any country, apart from the US and the Zionist regime, but warned against relying on European heads of state that "have raised the flag of hostility against the Islamic Republic".