The protest followed a government announcement on Friday that Covid-19 restrictions would be tightened to include a mask mandate for children over the age of 6 and an early closure of kindergartens and primary schools, from December 20.
The government statement said it strongly recommended limiting social contact and preferably meeting people outdoors.
Police used water cannons on some protesters who were seen throwing objects and attempting to dismantle barricades.
Brussels police had tweeted earlier calling for the dissolution of the demonstration. They later added: "From this moment on, we will proceed to arrest the troublemakers."
Sunday's demo comes two weeks after a similar protest turned violent, with police estimating a turnout of around 35,000 people.
Footage posted on social media showed the police using water cannons on protesters.
The protests in Belgium are far from being the only clashes between police and protesters at demonstrations over Covid-19 measures. In late November, two people were wounded after police in the Dutch city of Rotterdam fired warning shots.
In Austria's capital city of Vienna, pepper spray was used during one protest in November, and thousands of people gathered on Saturday to protest the country's coronavirus lockdown and government plans to make vaccinations compulsory from February.