The crash was reported at 4:44 p.m. at the intersection of Miles Avenue and Heritage Palms Drive, according to the Riverside County Fire Department.
Firefighters arrived on the scene to find the two vehicles along with five victims, two of whom needed to be extricated from the vehicles.
Three of the victims sustained major injuries, while the two others suffered moderate injuries, officials said. All five were taken to a hospital, with one taken by helicopter.
The cause of the crash was under investigation.