The PSNI said two vehicles collided on the Annadale Embankment at around 3pm on Friday.
The casualties, both aged in their 20s, have been taken to hospital where their condition has been described as critical.
Another two people are also receiving treatment in hospital but their injuries are not thought to be life threatening.
Police said the crash involved a silver-coloured jeep and a yellow Renault.
Anyone witnessed the accident is asked to contact the PSNI on the 101 non emergency number..