About 80,000 people marched peacefully down Jakarta's main streets on Sunday, some chanting "Israel is the terrorist".
Thousands of Indonesians also protested in the Central Java capital of Semarang, Lampung, Pekanbaru and Banda Aceh on Sumatra island as well as in South Sulawesi's capital, Makassar, unfurling banners saying "Save Al-Aqsa from raid of the Jewish".
The protesters rallied outside the US embassy in what the police said appeared to be the largest protest the city had seen in years.
"The US, Israel are the real terrorist," read a large banner
carried by protesters who yelled anti-Israeli slogans.
Some protesters in Banda Aceh and Makassar trampled on
Israeli flags while waving the Palestinian flag.
The protests were organised by the Justice and Prosperity Party, a rapidly growing Islamic-based political party whose clean image helped lead it to a strong showing in parliamentary elections last year.
The protest came one week after a Hamas leader appealed to "the entire Muslim world" to protect al-Aqsa, as up to 10,000 Palestinians formed a mass human shield at the al-Aqsa Mosque against any possible threat to the site by Israeli ultra-nationalists.
A group of extremist Jews in Israel called Revava, which opposes Israel's planned withdrawal from the Gaza Strip, has threatened to storm the al-Aqsa Mosque in July, when Israeli police and soldiers are to evacuate 9000 settlers from Gaza.