Acting on intelligence police stopped a Transit van on the northbound carriageway of the M74, near to Junction 13 at Abington, at around 4pm on Friday.
When they searched the vehicle they found around 20 kilos of what is believed to be herbal cannabis with an estimated street value of £300,000.
Two men, aged 21 and 43, have been arrested in connection with the seizure.
As part of their investigations, officers acting under warrant also searched a property in Albion Street, Coatbridge, North Lanarkshire.
They discovered more than three kilos of what is believed to be cocaine, worth an estimated street value of £325,000.
A 46-year-old woman has been arrested in connection with alleged drugs offences.
The three people are expected to appear at Lanark Sheriff Court in due course.