The northwestern Idlib region remains the largest populated area of Syria in the hands of insurgents fighting the Damascus government. In recent years, tens of thousands of fighters and civilians have fled there from parts of the country which the army has recaptured with the help of Russia and Iran.
Le Drian said Idlib now has some 2 million inhabitants, including hundreds of thousands of Syrians evacuated from rebel-held cities taken back by the Syrian regime.
"There is a risk of a new humanitarian disaster. Idlib's fate must be settled by a political process, which includes disarming the militias," Le Drian said in an interview with French weekly Le Journal du Dimanche.
Some insurgent officials have said they feared an onslaught against Idlib, which a senior Iranian official has indicated could be the next target.
He added that France would also keep a close eye on the situation in northeastern Syria, which was freed from Islamic State with French help.
"Let's not forget that our principal enemy remains Islamic State, as well as other terrorist groups which are currently regrouping in the east of the country," Le Drian said.
The insurgents controlling Idlib include both jihadist factions and nationalist FSA rebels. The dominant force there is Hayat Tahrir al Sham, an Islamist alliance spearheaded by the former al-Qaeda affiliate in Syria.