Video shows protesters retreat from the building after officers in riot gear began to walk toward them and fire what appeared to be pepper balls.
Officers are seen grabbing a protester with a bullhorn, leading to a scuffle.
DHS officers move in on protesters near Santa Ana federal building
Footage also shows another protester get hit in the face with a rubber bullet, leaving him bloodied. The protester falls to the ground and gets dragged by one of the officers.
The demonstration unfolded outside a downtown Santa Ana federal building that houses Immigration and Customs Enforcement field offices.
Protests have spread across the country following the deadly ICE shooting of Renee Good in Minneapolis. More protests against immigration enforcement are planned nationwide Saturday.
Santa Ana police did not report any arrests from Friday's protest.