The crash occurred shortly before 8:30 p.m. at 7th and Tatnall streets.
Police say the operator of the bike, described as a 21-year-old man, was travelling east on 7th street when his bike collided with a car that was heading south on Tatnall.
The cyclist suffered injuries to his head and hands.
Medics responded and transported the cyclist to Christiana Hospital for care.
Two occupants of the car suffered minor injuries and were transported to St. Francis Hospital for care.
Officers say off-road unregistered motorbikes have posed a major problem for police this summer.
There is no word on any charges at this time.