Emergency services were called to the B6042 Crags Road at around 4.45pm.
A Peugeot 106 travelling towards the A60 had collided with a Citroen C2 travelling towards Creswell.
Two children travelling in the Peugeot sustained fatal injuries as a result of the collision.
Witnesses are asked to call the Derbyshire Police witness line on 01773 572929.