"There is a humanitarian risk and also a security time-bomb," Le Drian told France Inter radio on Sunday.
"This is a very serious situation that can explode in a few days' time since clearly Bashar al-Assad's regime wants military reconquest."
The 2016 recapture of Syria's second city, Aleppo, was "nothing in terms of suffering and catastrophe compared to what could happen", Le Drian added.
Some 10,000 Islamist fighters are inside the last rebel bastion, according to the UN.
Le Drian estimates there are 700,000-800,000 refugees among the three million population.
Idlib is an "explosive crucible in all senses of the term", he said, warning that there was a risk of a "scattering" of the jihadists.
The minister also evoked fears that Assad regime might use chemical weapons and said France's response would be "the same as before" if that is the case.
France, the US and the UK launched air strikes against Syrian military facilities in April after what they said was a chemical attack by Assad's forces on the town of Douma.
President Emmanuel Macron has discussed the situation with Turkey's Recep Tayyip Erdogan by phone and will soon talk to Russia's Vladimir Putin, Le Drian said.
The two will meet Iranian leader Hassan Rouhani in Kazakhstan's capital, Astana, on 7 September to discuss the Syrian conflict.
"I hope that between them they will find a way to avoid this disaster," Le Drian said.