“Our doctrine rests on the fundamental interests of the nation," Mr Macron told public broadcaster France 2 on Wednesday.
"They are defined clearly and wouldn’t be directly affected at all if, for example, there was a ballistic nuclear attack in Ukraine, in the region."
It was the first time Mr Macron has discussed France’s nuclear deterrence doctrine regarding Ukraine in detail, but he said it was not good to talk about it too much.
Hints by Russian President Vladimir Putin that he could order the use of nuclear weapons in Ukraine have been widely condemned by western powers.
Mr Putin said after announcing the annexation of four occupied regions of Ukraine that Russia would use "all the forces and resources we have" to defend what Moscow claims as its territory.
But despite his threats, the US said last week there was no clear evidence that Mr Putin was on the brink of a nuclear launch.
Mr Macron said Mr Putin must "return to the table" to discuss peace in Ukraine and that he thought Kyiv would have to negotiate with him at some point.
"Today, first of all, Vladimir Putin must stop this war, respect Ukraine's territorial integrity and come back to the table for talks," he said.
Asked if he would back a Ukrainian offensive to recapture Crimea, which was annexed by Russia in 2014 in a move not recognised internationally, Mr Macron said that "at some point as the conflict develops", Russia and Ukraine "will have to come back to the table".
The Ukraine war latest - in pictures
"The question is whether the objectives of the war will only be reached by military means," he said, although "it's up to the Ukrainians to decide" what those aims should be.
When reminded that Ukraine no longer wanted to negotiate with Mr Putin, Mr Macron said: "I tell you that at some point … it will be necessary. That's why I have always refused maximalist positions."
He said France would supply air defence systems to Ukraine after Russia's wave of air strikes this week, which was aimed at "breaking Ukrainian resistance".
"We're going to deliver … radars, systems and missiles to protect them from these attacks," Mr Macron said.
He said France was also negotiating to send another six Caesar mobile artillery units.
Putin vows continued 'tough' attacks against Ukraine - video
He said the war had entered "an unprecedented stage" since the weekend because "for the first time all over Ukraine civilians have been killed … and electricity and heating facilities have been destroyed".
"The aim of the Russians these last few days has been to break, to shatter Ukrainian resistance," Mr Macron said.
He acknowledged that France was "unable to deliver as much as the Ukrainians ask for. I'm obliged to keep some for us to protect ourselves and our eastern flank [of Nato]".
The extra Caesar guns were made for Denmark, but talks are under way to redirect them to Ukraine.