The collision involving a silver Ford transit and a blue Ford Focus happened shortly after 10pm at the junction of the Moira Road and Ballydonaghy Road.
Two men aged 56 and 68 were taken to hospital for treatment for serious injuries.
The Moira Road has now reopened to traffic.
Police have appealed to anyone who witnessed the collision or was travelling on the Moira Road around the time of the collision to contact them on 0845 600 8000.
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