The crash occurred shortly before 8 p.m. at Plummer Street and Van Nuys Boulevard, according to the Los Angeles Fire Department.
Video from AIR7 showed a black car and a white car, both with major damage, at the scene. The white vehicle was halfway onto the sidewalk.
The 28-year-old man, who was in the white car, and the two pedestrians "are in at least serious condition and will be transported to local hospitals by LAFD paramedics," the Fire Department said in a statement.
Three patients from the other vehicle suffered minor injuries, the LAFD said.
The cause of the crash was under investigation.