To get to the speech, Secret Service agents lead Mr Trump across a motorway and had him enter through a side door.
Protesters repeatedly pushed through police barriers and held anti-Trump signs, piñatas and Trump dolls.
The Republican front-runner’s rallies have been violent in the past including an incident on Thursday.
A police car had its windows smashed as Mr Trump spoke inside a hall in the Orange County Fairgrounds in Costa Mesa. Some 20 arrests were made.
The Trump campaign had to cancel several rallies in March after hundreds of protesters threatened to disrupt events in Chicago and St Louis.
On Friday, Mr Trump made it to the stage and joked about the protesters, saying “that was not the easiest entrance I ever made.”
“I felt like I was crossing the border,” he said, and that he walked through “dirt and mud” to get to the building outside of San Francisco.
Many of the protesters outside his speech were arguing against his positions on immigration. He has made building a border wall with Mexico which he says Mexico would pay for.
He has also referred to Mexicans as “rapists” and criminals responsible for bringing illegal drugs into the US.
Mr Trump is extremely unpopular among Latino voters and California has a large Mexican-American population.
Protests are expected to continue until the California primary is held on 7 June.
Mr Trump has called himself the Republican “presumptive nominee” after a string of primary wins.
In terms of delegate support, the property tycoon is far ahead of his nearest rivals, Texas Senator Ted Cruz and John Kasich, the governor of Ohio.