The crash occurred near the intersection of Wilshire Boulevard and Manning Avenue shortly after 3 a.m.
Los Angeles police say the motorcycle t-boned the Nissan Sentra as the driver behind the wheel of the vehicle was attempting to make a left-hand turn on Manning Avenue.
"I looked out the window, I seen what happened and I came down to try to help. I seen the youngster in the backseat right here, passenger side. He was going into shock. The guy in the motorcycle he came to and he started trying to get up. People were telling him not to," one man told Eyewitness News at the scene.
Four college students, possibly from UCLA, were inside the vehicle at the time of the crash. They were returning home from getting something to eat, police said.
The victims were transported to Ronald Reagan UCLA Medical Center and Cedars-Sinai Medical Center. The motorcyclist and a second victim were listed in critical condition.
The driver of the Nissan Sentra has since been released from the hospital.
Investigators are working to determine how fast the motorcycle was traveling.
"When [the motorcyclist] passed me he had the bike going so fast, he was almost laying it down. I said there's no way he's going to be able to see somebody coming up over this hill, and sure enough by the time we got here this was the outcome unfortunately," a second man said.
Wilshire Boulevard was temporarily closed near Manning Avenue but has since reopened.