Initiated by President George W. Bush, the conference is expected to address the status of the Palestinian National Authority. Other Arab states have indicated they will attend the forum, although many remain skeptical.
"All the world's politicians are convinced that this conference is doomed to failure," Khamenei told local television. "The organizers hope the event will help them support the Zionist regime [Israel]."
Khamenei's statements echoed those of Iranian President Mahmoud Ahmadinejad, who said on Sunday that the forum would bring no benefits for the oppressed Palestinian nation and was only meant to bolster the Zionist occupiers.
The Iranian spiritual leader also said the Middle East forum had been called the autumn conference because "it is the autumn of their [U.S., Israel] hopes."
Iran, which does not recognize the state of Israel, is the only influential country in the region that has refused to attend.
The Annapolis conference is seen as a starting point for resuming peace negotiations between the Palestinians and Israelis after a seven-year hiatus.
Apart from Israeli Prime Minister Ehud Olmert, Palestinian leader Mahmoud Abbas and UN chief Ban Ki-Moon, 49 countries will be represented at the event. Members of the Arab League and Group of Eight industrialized nations, such as Britain, Russia, France, Germany, Canada, Japan, Italy, and the U.S. will also attend the event.
The International Monetary Fund and the World Bank have been invited as observers.
The conference will be preceded by a meeting of the Middle East Quartet of mediators - the U.S., Russia, the UN and the European Union - on Monday.