The global sweep involved police in Germany, Italy, the Netherlands and Belgium working together against the powerful organised crime syndicate based in southern Italy.
European law enforcement agencies jointly launched Operation Pollino in 2016, looking to put a dent in the 'Ndrangheta's criminal operations.
Eurojust said the massive operation was the biggest of its kind in Europe.
Officials said by midday of the operation, nearly 4,000 kilos of cocaine and hundreds of kilos of other drugs were seized.
Police seized four tonnes of cocaine, 120 kilos of ecstasy and around 2 million euros ($2.3 million) in cash from locations including Italian restaurants and ice cream parlours.
Federico Cafiero De Raho, Italy's chief anti-mafia prosecutor, hailed the "extraordinary nature of this operation", but warned that the organization is "extremely powerful and extremely rich", so they are far from defeated.
Italian police arrested Settimo Mineo, 80, Tuesday, who authorities believe to be the lead Mafia boss who replaced the late Salvatore Riina.
The 'Ndrangheta - whose heartland is the southern Calabria region - is one of the three main mafia groups in Italy, along with the Sicilian mafia and the Camorra.
He added, groups of the 'Ndrangheta and its allies, have infiltrated the ports around Europe and "polluted" lawyers and accountants in many countries on their payrolls.
Dutch NOS television said the 'Ndrangheta were mainly active in the Netherlands in drug smuggling through the country's huge flower export market.
Eurojust said Italian authorities arrested 41 suspects, mainly in Calabria.
Police arrested dozens of people in Europe and South America in a "decisive hit" against Italy's notorious 'Ndrangheta mafia group, officials said Thursday. The focus was on the western state of North Rhine-Westphalia, which borders the Netherlands and Belgium, and Bavaria to the south.
Italian media said key organised crime family members were targeted.
Five suspects were arrested in the Netherlands, where prosecutors got the ball rolling for the investigation in 2014 with probes into two Italian restaurants, and more were detained just over the border in Belgium.
The coordinated operation resulted in the arrest of some 90 suspected mobsters and is the product of two years of intelligence gathering.