In an operation involving more than 100 officers, eight houses were searched as part of Operation Archerfish.
Homes in Selkirk, Kelso, Galashiels, and Hawick were targeted in the investigation which uncovered illegal drugs worth about Â£3,750.
Police also recovered about Â£1,200 in cash in the early morning raids.
Two men, aged 32 and 34, have been arrested and charged under the Misuse of Drugs Act. They are expected to appear at Jedbrgh Sheriff Court on Friday.
Officers are also looking for a man in relation to cannabis cultivation and further inquiries are being carried out for other drug supply offences.
Police Scotland said the operation has seriously disrupted the drug supply networks in the Borders and removed a "significant quantity" of controlled drugs.
Det Ch Insp Stephen Healy, of the specialist crime division, said: "This operation was devised due to feedback from the local community.
"Over 100 officers took part in today's executive day of action and we have sent a strong message to those in our community who peddle harmful substances to the public."
The raids were supported by Scottish Borders Council and NHS Borders.
Dr Eric Baijal, joint director of public health for the agencies said: "Many local people will not think there is a significant drug problem in the area, however NHS Borders and other agencies in the Scottish Borders are at the front line and see the impact of substance misuse on a daily basis.
"Drugs have a devastating impact on people's health, well-being and life in general, and we have a range of confidential support services available for adults and young people."
Police in the Borders have seized a quantity of drugs and cash during a series of raids across the region.