"Since day one I have considered Daesh (the Islamic State group) to be our principal enemy, and I have never made the ousting of Bashar al-Assad a condition of our diplomatic or humanitarian action in Syria," he said.
But he accused Assad of "creating thousands of refugees" and "massacring his own people".
Meanwhile Macron blamed European Union dependene on the US and reiterated that he would put forward new proposals for the European Union to boost its security, saying the bloc must stop depending on American might.
"Europe can no longer rely on the United States for its security. It is up to us to guarantee European security," he said in a speech to relaunch his diplomatic agenda.
His proposals will be unveiled "in the coming months", Macron told an audience of some 250 diplomats, lawmakers and international relations experts gathered to mark the return from the summer break.
"I want us to launch an exhaustive review of our security with all Europe’s partners, which includes Russia," he added.
Macron’s comments came after a string of gestures from US President Donald Trump distancing himself from traditional NATO allies.
Trump has repeatedly called into question the Western alliance’s core commitment to mutual defence, while complaining that the US spends too much on military support for Europe.
Macron came to power last year vowing to overhaul the EU and has pushed for deep political reforms -- including a separate budget for the eurozone -- which have so far met with lukewarm support.
Reporter's code: 50101