The car was stopped in Duncrue Street in Belfast on Wednesday evening at 20.15 GMT.
Police seized suspected herbal cannabis and cocaine thought to be worth a substantial amount.
The men, aged 28 and 31, have both been arrested for possession and supply-of-drug offences.
Det Insp Tom McClure from the PSNI's Reactive and Organised Crime Branch said: "I believe that this intervention has struck a blow to the activities of an organised gang involved in serious drug criminality."
Police say the arrests of two men following the seizure of drugs from a car in Belfast have dealt a blow to organised crime.