Officers have seized 28,840 illegal cigarettes and more than 15kg of tobacco with a potential retail value of around £21,000 from a house in Chesterfield.
Police and Derbyshire County Council's trading standards team searched the property in Newbold last Thursday.
As well as the illegal cigarettes and tobacco, they also seized £4,000 in cash.
Sergeant Matt Adams, of the Newbold and Brockwell Safer Neighbourhood Policing Team, said: "The use of illegal cigarettes and tobacco can put people's health at risk and the sale of them can sometimes be linked to more serious organised crime groups.
"We are grateful for the support of our local communities and our team will continue to work with partner agencies to investigate and act on information passed to us about counterfeit and illegal products to ensure we keep consumers safe and stand up for legitimate local traders."
A 44-year-old man and a 43-year-old woman are due to be questioned in relation to the goods by the council's trading standards team which is leading the investigation.
Councillor Carol Hart, the council's cabinet member for health and communities, said: "This is another successful operation for our trading standards team which demonstrates our clear message to traders who sell illegal tobacco that we will not tolerate it - they will be caught.
"We will continue to work with Derbyshire police to take a hard line against retailers who break the law, risk people's health and threaten the livelihoods of honest businesses.”