Clooney had departed his Costa Corallina hotel on what's variously described as a motorbike or scooter when he was hit by a auto around 8:15am local time.
The 57-year-old has been taken to hospital but is understood not to be seriously injured.
Clooney is a Northern Kentucky native.
A spokesman for the Italian Carabinieri told the Press Association: 'At 8.15am George Clooney was riding his scooter on the State Road 125 towards Olbia from Puntaldia.
The John Paul II hospital in Olbia confirmed Clooney was treated there and released after a few hours.More news: Cristiano Ronaldo rejects huge Chinese Super League contract offer
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An ambulance later took Clooney to the nearest hospital, according to Cicognani.
Clooney is in Sardinia to film a miniseries based on Joseph Heller's book "Catch 22", the news agency said.
Pictures from George Clooney's motorcycle crash have emerged, showing the dramatic scene in Sardinia.
Immediately after the crash, Clooney was transported to a nearby hospital.
George and Amal Clooney just donated $100,000 to help migrant children separated from their parents.
Clooney is now filming TV drama Catch-22 on the Italian island.