Donald Trump has warned Bashar al-Assad and the Syrian president’s allies Iran and Russia not to “recklessly attack” in the rebel-held Idlib province, warning that hundreds of thousands of people could be killed.

“The Russians and Iranians would be making a grave humanitarian mistake to take part in this potential human tragedy. Hundreds of thousands of people could be killed. Don’t let that happen!” Trump tweeted on Monday night.

Up to three million people in the region are bracing for imminent attack by Russian forces who sense victory in one of the last parts of Syria still out of regime control. On Friday the Russian navy manoeuvred in the nearby Mediterranean, while other nations also took positions; the Turkish army sent an armoured convoy deep into Syria, Iranian-backed militias mobilised to the south and the Syrian army was placed on high alert.

The northern province and surrounding areas are the last major enclave held by insurgents fighting Assad, who has been backed by both Russian and Iranian forces in Syria’s seven-year-old civil war.

Trump has sought better relations with Russia since taking office in 2017 but the US has been unable to rein in Moscow’s military and diplomatic support for Assad.

The US secretary of state, Mike Pompeo, said on Friday that Washington viewed any government assault on Idlib as an escalation of Syria’s war, and the state department warned that Washington would respond to any chemical attack by Damascus.

Earlier on Monday, Iran called for militants to be “cleaned out” of Idlib as it prepared for talks with Syria and Russia about confronting the last major enclave held by rebels opposed to Assad.

The Iranian foreign minister, Mohammad Javad Zarif, visited Damascus to discuss plans for an upcoming summit between the leaders of Iran, Russia and Turkey, which Tehran will host on 7 September to discuss Idlib, Iran’s Fars news agency reported.

Turkey, which has long supported anti-Assad rebels, has cooperated with Russia and Iran on talks over Syria in recent years and has troops in the Idlib region on an observation mission.

Last week Iran’s defence minister travelled to Damascus and signed an agreement for defence cooperation between the two countries with his Syrian counterpart.

Reuters contributed to this report