Police are warning motorists to avoid Carr Lane Dronfield Woodhouse after the crash this morning at 8.25 am.
An Audi Q2 ended up on its roof after the collision involving a Seat Ibiza and Ford Transit van.
Firefighters from Dronfield and Low Edges made the scene safe as East Midlands Ambulance Service attended to casualties.
There are no details of injuries at present.
Derbyshire Police said the incident left an oil spill on the road.