The protesters threw stones and bottles at the police, who responded with tear gas and stun grenades.
Several Palestinians are reported to have been detained, including a former minister, Hatem Abdulqader.
The Israeli police said they had closed the compound because Palestinians had planned a mass gathering there.
Palestinians say they are trying to protect the site, known to Muslims as the Haram al-Sharif and to Jews as the Temple Mount, from Jewish hardliners, who they fear intend to desecrate it.
There were reports of three arrests, and several police and protesters were slightly injured.
Police closed off the sites after mosque loudspeakers in Jerusalem's Old City urged people to gather there, following rumours that Jewish settlers were to be allowed into the compound.
"We closed the access to the Temple Mount following incitations to violence," police spokesman Micky Rosenfeld told AFP news agency.
The incident follows similar protests a week ago in which 30 people were injured.
Security has been boosted at the compound as Jews attend prayers for the seven-day Feast of Tabernacles at the Western Wall.
In the past the compound has been a flashpoint for Israel-Palestinian violence, notably after the visit of then Israeli opposition leader Ariel Sharon in 2000.
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