The duo were travelling in a car with Indian registration number - UP 85 0133 - and were heading towards the Indo-Nepal border town of Raxaul from Hetauda, when they were arrested.
Nepal Police said the arrests were made during a security check, following a tip-off.
They said the huge cache of marijuana was hidden inside a false box in the car.
The two men were identified as Asha Kuwar, 40, of West Champaran district and Ashok Kumar Nalewat, 25, of Bulkroad Bihiya, Bhojpur district, both in Bihar.