The accident - which involved a Mazda Premacy car and a white Ford transit van - took place near Junction 24a of the M1 at about 2am.
An 87-year-old, who was driving the Mazda, and a 27-year-old, who was a passenger in the van, were pronounced dead at the scene.
A police spokesman said the van driver was taken to Queens Medical Centre, where he remains in a stable condition.
Before the collision, police had received reports of a car travelling the wrong way along the southbound carriageway.
Emergency services have closed off the southbound carriageway between junctions 25 and 24
It is expected to remain closed for some time.
A spokesman for Nottinghamshire Police said: “Drivers are asked to avoid the area if possible. Thank you for your patience.”
Anybody with information about the incident, or saw either vehicle prior to the collision, should call Leicestershire Police on 101 quoting incident 23 of 12 October 2015.