In a statement, Villaraigosa said "every country has a right to defend itself against attacks from a foreign enemy. Every nation is obligated to beat back forces dedicated to its destruction. And Israel cannot sit silently while innocent civilians are attacked."
He also asked people to pray for peace.
"During this trying time in the Middle East, I hope all people -- regardless of race, religion or creed -- will join me in praying for peace, for an end to hostilities, and for a halt to violence on all sides," he said.
After a week of air strikes, Israel launched a ground offensive into Gaza on Saturday, in response to escalating rocket attacks by Hamas, an Islamic group elected by Palestinians that has never acknowledged the right of Israel to exist, and which the United States considers to be a terrorist organization.
Last year, Villaraigosa visited Israel, including the town of Sderot, which is near Gaza and a frequent target of unguided missiles fired by Hamas.
Israel has been criticized for the massive military response, which has resulted in the deaths of hundreds of Palestinians, and on Sunday, the ANSWER Coalition and L.A. Jews for Peace held protests in Westwood and Anaheim.
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Protester Ian Thompson told CBS2 that he is not Palestinian, "but I feel like I'm Palestinian today and every day I see civilians and women and children being bombed indiscriminately."
"They're facing a massacre in Gaza," Palestinian protester Mahmoud Al Khalili told the TV station. "I think this is an attack on democracy. People elected Hamas in 2006."
A Los Angeles Jewish official said Israel's incursion must continue until Hamas stops firing rockets.
"Israel is saying no more cease-fires if 'cease-fire' means that Hamas gets a chance to violate the cease-fire by bringing upgraded weapons from Hezbollah and from Iran so that they can now in the next attack hit Tel Aviv and Jerusalem," Rabbi Marvin Hier of the Simon Wiesenthal Center told ABC7. "Israel is saying to the world, 'Been there, done that."'
Meantime, Islamic Relief USA, based in Buena Park, has started a fundraising effort to provide medicine and food to Gaza residents.
"The children are terrified. Adults are unable to provide them with security or warmth. Hospitals are stretched out of the limits. We need blood and medicine and surgical equipment," said Dr. Eyad El-Sarraj, head of Gaza's mental health program.
More protests are scheduled for later this week.