Officers from the Scottish Crime and Drug Enforcement Agency (SCDEA) and Strathclyde Police searched property in High Street in the Merchant City.
Police found 20kg of cannabis worth an estimated street value of £100,000.
Three men, aged 27, 28 and 27, were arrested and charged with offences under the Misuse of Drugs Act (1971). They were expected to appear at Glasgow Sheriff Court today.
Detective Chief Superintendent Athol Aitken, head of Investigations for the SCDEA said: "Cannabis continues to be the most widely misused controlled drug in Scotland.
"As a result of this operation a significant quantity of cannabis has been prevented from reaching our streets and affecting the lives of ordinary people and families.
"This level of drug dealing is undertaken by serious organised criminals whose only focus is on profit and power over individuals and communities.
"The Scottish Crime and Drug Enforcement Agency works in partnership with Scotland's police forces and other agencies to detect serious drug dealers but also to reduce the harm to our communities.
"The arrests and recovery of drugs on Monday night is an example of this and again emphasises our determination to tackle serious organised crime at all levels."
The seizure comes less than a week after the recovery of another significant drugs haul in the north of the city by the SCDEA when officers seized eight kilograms of heroin worth more than half a million pounds along with six kilograms of cannabis resin with an estimated street value of £30,000.
Four members of a cross-border crime group were arrested as a result of the SCDEA activity.