Shaikh Muhammad Sayyid Tantawi on Tuesday condemned reports of Jewish extremists planning to attack Al-Aqsa Mosque compound in Jerusalem.
"These threats cannot be envisaged either mentally, legally, religiously or morally," he told the official news agency MENA.
The Shaikh, who heads the leading Islamic scholarly institution, al-Azhar, warned Israel and the international community that an attack on the mosque could destabilise the region and create global upheaval.
"Only a mentally deranged person would [threaten] such a thing," said Tantawi, who called on Muslims around the world to unite to challenge the threat.
Israeli media reported on Sunday that authorities fear Jewish hardliners and fundamentalists could be planning an air attack on Al-Aqsa Haram compound, in an attempt to derail government plans to uproot settlers from the Gaza Strip.
Israel's Public Security Minister Tzahi Hanegbi had earlier said hardline Jewish groups might be planning to carry out attacks on the two most sacred Islamic shrines in occupied East Jerusalem.
The secretary general of the Organization of Islamic Conferences (OIC), Abd Al-Wahid Bilkaziz, warned on Tuesday that any damage done to al-Aqsa mosque in Jerusalem could trigger "widespread disturbance".
"Any harm to al-Aqsa mosque will cause widespread disturbances with unpredictable consequences and which will cause grave danger to international peace and security," said Bilkaziz in a statement.
Could Israeli groups trigger a war
by storming the Noble Sanctuary?
Bilkaziz said Israel would be held responsible for any attack on the Noble Sanctuary, al-Haram al-Sharif, "because it is the occupying authority and has a duty to protect religious places in accordance with international law."
"Any harm will cause an explosion of anger from Muslims across the globe," he added.
The OIC, which was funded in 1969 and includes 56 member states, aims to promote international solidarity among Muslims and political, economic, and social cooperation between member states.