The accident happened just before 8 p.m. near the intersection of Ventura and M Street.
Fresno police say it appears a Saturn made a left turn in front of a Toyota 4Runner. The SUV flipped upside down, leaving the 42-year-old female driver and her 43-year-old husband pinned inside.
Firefighters used special equipment to get them out, and both were taken to Community Regional Medical Center with moderate injuries. The other driver was not hurt.
Officers say alcohol or drugs do not appear to be factors in the crash.