"If we destabilise the region because of Iran, we will nurture the next terrorist movements that will be born in the region because they feed on the latent conflict between Sunni and Shia," Macron warned in an interview in the Journal du Dimanche newspaper.
After meeting Trump in Washington last month, Macron was pessimistic about the prospects of Trump reendorsing the Iran nuclear deal, despite his appeals to do so and those of the leaders of other signatory countries.
Trump is under strong pressure from Israel not to do so but there is increasing tension between Sunni-Muslim-led Gulf countries, notably Saudi Arabia, and the Shia-led Islamic Republic.
In another interview, with Germany's Der Spiegel, Macron said, "We would be opening Pandora's box, there could be war."
Macron said he discusses with Trump "while knowing perfectly that his foreign policy is always dictated by domestic considerations" and that on the Middle East the US leader is "divided between his desire to pull out and his anti-Iranian prism".
The French leader repeated his claim to have persuaded Trump to commit US forces to last month's air strikes on Syria, a "very complex and successful operation, remarkably well coordinated by three allies".
Although the two men have numerous differences - over Iran, climate change and protectionism, notably - and US-France relations have been strained this weekend by Trump's remarks on the 2015 Paris attacks, Macron told the paper he believes that transatlantic relations can be remodelled by "concentrating on the political-military and the fight against terrorism".