The Campania region, which includes Naples, announced it would go into lockdown on Friday as the number of COVID-19 cases soared.
Demonstrators threw flares and other missiles at police who responded with tear gas.
There were unconfirmed reports protestors stormed local government offices.
Jakub Wondreys posted a video of the disorder on Twitter with the caption: “Big anti-regional government COVID-19 restrictions protests are happening right now in Naples, Italy.
“The situation seems to be out of control, thousands of people in the streets fighting with police, also stormed the regional government offices.”
Footage posted on social media showed thousands of demonstrators, many wearing masks to protect against coronavirus, marching through the city.
Many were chanting “freedom, freedom, freedom” during their procession.
RadioSavana, which has been covering the protests, tweeted: “All of Naples in revolt!
“The population is mass protesting against the lockdown.
“At 11.00 pm the curfew order is triggered, the images are live: civil disobedience in progress.”
They later added: “Protests also underway in Salerno, Nocera and other cities of Campania.”
The number of COVID-19 cases in Italy has risen seven-fold since the beginning of October.
Vincenzo De Luca, President of the Campania region, has ordered a night-time curfew and the closing of schools.
On Facebook he posted: “Current data on the contagion make any kind of partial measure ineffective. It is necessary to close everything, except for those businesses that produce and transport essential goods.
“We need to make one last effort to get things under control. We need to shut everything down for a month, for 40 days.”