In a telephone call with King Abdullah II of Jordan, which has custodianship rights over the contentious holy site, Hollande expressed his "deep concern" over clashes between Palestinians and Israeli police over the past three days.
Rioting erupted at the site sacred to both faiths as Jews celebrated their new year between Sunday evening and Tuesday evening.
The compound is the third-holiest site in Islam and home to the Dome of the Rock and Al-Aqsa mosque. It is also the holiest site in Judaism which venerates it as the Temple Mount.
Israel seized east Jerusalem, where Al-Aqsa is located, in the 1967 Six-Day War and later annexed it in a move never recognised by the international community.
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Muslim protesters fear Israel will seek to change rules governing the site, with far-right Jewish groups pushing for more access to the compound.
Netanyahu has repeatedly said he is committed to the "status quo", but Palestinians remain deeply suspicious.
Hollande said any change in the status quo would lead to "a great risk of destabilisation".
"These events once again illustrate the importance of a swift return to talks to work towards a resolution of the conflict."