One of two missiles fired hit a bodyguard's car in front of Mr Barghouti, who heads Palestinian leader Yasser Arafat's Fatah movement in Ramallah.
Palestinian officials said it was the latest in a series of Israeli attempts to assassinate prominent local activists and militants in the West Bank and Gaza.
The Israeli army made no immediate comment on the incident, but Israeli security sources quoted by Reuters said missiles had been fired at the convoy from the nearby Jewish settlement of Psagot.
The target was the car of Muhanad Abu Halaweh, a member of Mr Arafat's presidential bodyguard Force-17, the source said.
Mr Barghouti later told Associated Press that he and his companions might have been killed, if the first missile had not given them time to run away from the car.
"This is a new crime after the massacre at Nablus," Mr Barghouti said, referring to a strike on Tuesday which killed eight Palestinians including two Islamic militant politicians and two young boys.
"It is clear this is all-out war. They are trying to silence the fires of the intifada. But our response will be to escalate the resistance."
Lucky escape
The cars had reached Mr Barghouti's offices in Ramallah when the first missile hit the road directly in front of the first car. The second missile scored a direct hit, reducing the car to a metal frame.
An eyewitness saw Mr Barghouti's entourage passed in front of his house just before the attack.
"Marwan came down the road in his jeep and waved at us, as soon as he got to the end of the road I saw a missile flying towards me," said Khalid Eisa.
"We heard the second one and ran up to the house, people began shouting, that's all I remember," he added.
Hospital sources said say one of Mr Barghouti's aides sustained burns to the face and an elderly man who was walking nearby was also injured.
Marwan Barghouti's reputation as a hardline opponent of Israel's occupation in the West Bank and Gaza has grown since the beginning of the latest Palestinian intifada, or uprising.
He first emerged as a popular student leader during the first intifada between 1987 and 1992 and has been tipped by some commentators as a possible successor to Yasser Arafat.