The crash, involving a Renault Clio and a Fiat Punto, happened at about 7.30am on Codnor Lane, Riddings, near the Golden Valley caravan site.
A 65-year-old woman, who was a passenger in the Punto, was pronounced dead at the scene.
A Derbyshire police spokesperson said: "Her family has been made aware and our thoughts are with them at this time.
"Two people were taken to Queen’s Medical Centre, one with serious injuries, while two more people with minor injuries were taken to Kings Mill Hospital.
"The road was closed for several hours while a collision investigation was carried out. It was reopened at about 3pm."