"All indications ... tell us today that chlorine is being used by the regime at present in Syria," Le Drian said in an interview on Wednesday morning.
But he added that "we haven't completely documented this" so "we have to remain cautious".
UN war crimes investigators said Tuesday that they were studying a number of reports that chemical weapons have been used in the rebel-held zones of Eastern Ghouta, near Damascus, and in the north-western Idlib Province in recent weeks.
The United States said this week there was "obvious evidence" of chlorine gas attacks, including in Eastern Ghouta, recently.
Asked how France would react if there was proof that what President Emmanuel Macron has called a "red line" has been crossed, Le Drian pointed to the "partnership against impunity" agreed by two dozen countries in January to ensure that perpetrators of chemical attacks in Syria are held accountable.
Iran criticised, not Turkey
The minister called on "everyone who has no business being in Syria to leave, specifically naming the Lebanese Hezbollah group and "Iranian militias".
But he refrained from condemning Turkey's military offensive against Kurdish YPG rebels, who were backed by the US-led coalition as the most effective opposition to IS.
He can "understand" that Ankara wishes to "ensure the security of its borders", he said, while warning against killing civilians.
"The Kurds have been absolutely exemplary and decisive in the capture of Raqqa," he said. But he only named the Iraqi Kurdish Peshmerga and not the YPG in that context.
French jihadists to be judged in Syria, Iraq
The Kurdish forces have told France they are holding about 100 of its citzens in Syria, Le Drian said, adding that the "local legal authorities", who are "not automatically Kurds but the Syrian democratic forces too" would deal with them.
"They will not be repatriated insfar as they are combatants, so they are enemies," he said.
The French government is reluctant to repatriate jihadists but has said it would react if any national are given a death sentence.
Six families are being held in Iraq, Le Drian said.