Bourne Police and Fire crews responded to the scene at the intersection of Meetinghouse Lane and Old Plymouth Road just after 2:30 p.m.
A Medflight crew flew one man to a Boston hospital.
The other man was taken to Beth Israel Deaconess Hospital in Plymouth.
According to Sgt. Jonathan MacDougall of the Bourne Police Department, both men hospitalized were riding the motorcycle.
The accident is still under investigation.