Police in the southeastern city fired teargas and arrested several people after several hundred demonstrators started throwing objects, burning rubbish bins and trying to enter areas where protests have been banned.
Altogether about 2,000 protesters had gathered on the Allee Jean Jaures, a wide avenue in the city center and on nearby side streets.
Activist groups had said on social media networks that Toulouse would be the focus for the 22nd round of demonstrations, prompting city mayor Jean-Claude Moudenc to express concern ahead of Saturday's protests.
Marches in Paris and elsewhere were largely peaceful by early afternoon, but the protests continue to put pressure on Macron. He has vowed to announce a series of measures aimed at easing discontent in the country.
The protests, named after the high-visibility safety jackets worn by demonstrators, began in November to oppose fuel tax increases.