The two men, aged 41 and 38, have been arrested on suspicion of possession of Class B controlled drugs and possession of Class B controlled drugs with intent to supply.
They both remain in police custody at this time.
The PSNI, working in partnership with the National Crime Agency (NCA), stopped a vehicle in the Dargan Road area of Belfast on Tuesday evening, just before 7.20pm.
Detective Inspector Shaw said: “Police stopped a vehicle in the Dargan Road area just after 7.20pm yesterday (Tuesday).
“A large quantity of suspected herbal cannabis, with an estimated street value of £375,000, was seized from the vehicle during the proactive operation.
“This search, seizure and arrest was conducted to target organised criminality and our ongoing commitment to address the criminality linked to drug importation, supply and use that often results in drug debts, drug addiction and drug-related deaths within our communities.
“I have no doubt this was destined for the streets of Northern Ireland with the potential for unimaginable harm and the funding of wider criminality.
“Through Operation Dealbreaker, and the multi-agency efforts of the Organised Crime Task Force, we will continue to carry out operations, to break the cycle of those who seek to cause harm through the illegal importation and supply of drugs in Northern Ireland, and to dismantle the organised criminals who profit from this incredibly harmful activity.”
Detective Inspector Shaw continued: “I appeal to anyone with information about illegal drug use or supply, to call police on the non-emergency number 101.
“Alternatively, you can submit a report online using our non-emergency reporting form via http://www.psni.police.uk/makeareport/.
“The independent charity Crimestoppers can also be contacted anonymously on 0800 555 111 or online at http://crimestoppers-uk.org/.
“To anyone who thinks they might have a problem with alcohol and/or drugs and would like to get help please visit www.drugsandalcoholni.info for information on support services near you.
“There is also a range of services available if you are affected by someone else’s drinking and/or drug misuse.”