The police charged the supporters with batons and lobbed tear gas shells.
A few hundred Khan supporters gathered outside his house after a police team arrived from Islamabad to arrest him on a court order, government spokesman Amir Mir told Reuters.
Khan's Pakistan Tehreek-e-Insaf (PTI) workers started the violence, which injured several police officials, Mir said, adding, "If Imran Khan ensures his presence in the court, it will be good, otherwise the law will take its course."
Khan called on his supporters to stand up for the supremacy of law and fight for true independence.
"Police have come to arrest and send me to jail," he said in a video recorded statement posted by his Twitter handle.
"If something happens to me, or sent to jail, or they kill me, you've to prove that this nation will continue to struggle even without Imran Khan."
Mir said the government has called out paramilitary forces to control the situation.
Several of Khan's supporters were injured when the police resorted to tear gas shelling, witnesses said.
Similar clashes took places last week.
"We have come here just for the compliance of the court order," deputy inspector general of police Syed Shahzad Nadeem told reporters.
The workers started pelting the police with stones and bricks, and in response police directed a water cannon at them and in some cases baton charged them, he said.
Live TV footage showed the supporters also using sling-shots and attacking the police with bricks and sticks.
"Our understanding is that the police can't arrest Imran Khan because he has secured a protective bail from a high court," his aide Shah Mehmood Qureshi told reporters.
The court in Islamabad had issued the arrest warrant in a case against Khan for unlawfully selling state gifts while in power from 2018 to 2022, his aide Fawad Chaudhry told Reuters.
The former prime minister has been embroiled in several court cases since his ousting early last year in a parliament vote of confidence.
He has been demanding snap polls in protest rallies across the country, a move his successor Shehbaz Sharif has rejected while saying the elections would be held as scheduled later this year.
Khan was also shot and wounded in one of these rallies.
