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The envoy said eastern Aleppo risked joining the ranks of the 20th century's worst tragedies including the Srebrenica massacre and the Rwandan genocide.
His plea comes two weeks into an all-out government assault on opposition parts of Aleppo following the collapse of a short-lived truce negotiated by Russia and the United States.
Diplomats said the UN Security Council would hold an emergency meeting on Syria Friday, at the request of Russia, with De Mistura expected to brief the council via videoconference from Geneva at 1400 GMT.
President Bashar al-Assad, meanwhile, warned rebels in Aleppo that unless they agreed to a deal with the government, his forces would have "no option" but to expel them from the city.
Loyalists have made significant advances in the Bustan al-Basha district near the centre of Aleppo, divided between government fighters in the west and rebels in the east, said the Syrian Observatory for Human Rights.
Observatory director Rami Abdel Rahman said it was the biggest and most significant advance inside the city since 2013.
The offensive by Assad's forces has seen rebel-held areas pounded relentlessly with air strikes, barrel bombs and artillery fire that the Observatory says have killed more than 270 people.
- Army 'gimmick' -
On Wednesday, the army said in a surprise announcement it would reduce its bombardment "to allow civilians who want to leave to reach safe areas".
"Anyone who does not take advantage of the opportunity to lay down their arms or leave will meet their inevitable fate," it said.
The Observatory reported fewer air strikes but heavy clashes on several fronts including Bustan al-Basha on Thursday, with the army now controlling key vantage points and half the neighbourhood.
Regime forces also seized buildings on the edges of the nearby Sakhur district, it added.
And 11 people were killed in rebel rocket fire on the government-controlled district of Al-Jamiliyeh, the Observatory said.
State news agency SANA earlier said at least eight people were killed and dozens wounded there.
Analysts dismissed the army announcement.
"The regime and its allies have made a decision to conquer as much of eastern Aleppo as possible and they're moving ahead on that," said Emile Hokayem of the International Institute for Strategic Studies.
"I think such announcements are actually marginal. They are a PR gimmick."
Syria expert Thomas Pierret said the move could be intended to undercut growing international pressure for action over the plight of civilians in east Aleppo.
The bombardment has damaged or destroyed several hospitals, including the largest facility serving the more than 250,000 remaining residents, who have been under near-continuous siege since mid-July.
"A temporary halt or reduction of bombings could prevent interventionists from gaining further influence," said Pierret, a lecturer at the University of Edinburgh.
- French-drafted UN resolution -
Washington said this week it was suspending talks with Moscow on Syria over Russia's involvement in the Aleppo assault.
But the US acknowledged Secretary of State John Kerry had called his Russian counterpart Sergei Lavrov to discuss Syria despite the announcement.
Moscow blames Washington for the truce's collapse and has shown no signs of easing its support for Assad.
De Mistura warned the ongoing assault would have dire consequences: "In maximum two months, two-and-a-half months the city of eastern Aleppo may be totally destroyed."
He urged fighters from the former Al-Nusra Front, now known as Fateh al-Sham Front after breaking with Al-Qaeda, to leave Aleppo under a deal to halt the regime's attack on the city.
"If you decide to leave with dignity... I am personally ready to physically accompany you," said the envoy.
Russia said it was "ready to work" on a French-drafted UN resolution calling for a ceasefire in Aleppo.
More than 300,000 people have been killed since the conflict began with fierce repression of anti-government protests in March 2011.
It has since evolved into a complex multi-front war that has drawn in regional and international forces including, most recently, Turkey.
Ankara launched an offensive on August 24, saying its forces and allied rebels would fight both the Islamic State group and Kurdish militia in northern Syria.
Thursday, at least 29 rebels involved in Ankara's operation were killed in a blast claimed by IS at the Atme border crossing with Turkey, the Observatory said.
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His plea comes two weeks into an all-out government assault on opposition parts of Aleppo following the collapse of a short-lived truce negotiated by Russia and the United States.
Diplomats said the UN Security Council would hold an emergency meeting on Syria Friday, at the request of Russia, with De Mistura expected to brief the council via videoconference from Geneva at 1400 GMT.
President Bashar al-Assad, meanwhile, warned rebels in Aleppo that unless they agreed to a deal with the government, his forces would have "no option" but to expel them from the city.
Loyalists have made significant advances in the Bustan al-Basha district near the centre of Aleppo, divided between government fighters in the west and rebels in the east, said the Syrian Observatory for Human Rights.
Observatory director Rami Abdel Rahman said it was the biggest and most significant advance inside the city since 2013.
The offensive by Assad's forces has seen rebel-held areas pounded relentlessly with air strikes, barrel bombs and artillery fire that the Observatory says have killed more than 270 people.
- Army 'gimmick' -
On Wednesday, the army said in a surprise announcement it would reduce its bombardment "to allow civilians who want to leave to reach safe areas".
"Anyone who does not take advantage of the opportunity to lay down their arms or leave will meet their inevitable fate," it said.
The Observatory reported fewer air strikes but heavy clashes on several fronts including Bustan al-Basha on Thursday, with the army now controlling key vantage points and half the neighbourhood.
Regime forces also seized buildings on the edges of the nearby Sakhur district, it added.
And 11 people were killed in rebel rocket fire on the government-controlled district of Al-Jamiliyeh, the Observatory said.
State news agency SANA earlier said at least eight people were killed and dozens wounded there.
Analysts dismissed the army announcement.
"The regime and its allies have made a decision to conquer as much of eastern Aleppo as possible and they're moving ahead on that," said Emile Hokayem of the International Institute for Strategic Studies.
"I think such announcements are actually marginal. They are a PR gimmick."
Syria expert Thomas Pierret said the move could be intended to undercut growing international pressure for action over the plight of civilians in east Aleppo.
The bombardment has damaged or destroyed several hospitals, including the largest facility serving the more than 250,000 remaining residents, who have been under near-continuous siege since mid-July.
"A temporary halt or reduction of bombings could prevent interventionists from gaining further influence," said Pierret, a lecturer at the University of Edinburgh.
- French-drafted UN resolution -
Washington said this week it was suspending talks with Moscow on Syria over Russia's involvement in the Aleppo assault.
But the US acknowledged Secretary of State John Kerry had called his Russian counterpart Sergei Lavrov to discuss Syria despite the announcement.
Moscow blames Washington for the truce's collapse and has shown no signs of easing its support for Assad.
De Mistura warned the ongoing assault would have dire consequences: "In maximum two months, two-and-a-half months the city of eastern Aleppo may be totally destroyed."
He urged fighters from the former Al-Nusra Front, now known as Fateh al-Sham Front after breaking with Al-Qaeda, to leave Aleppo under a deal to halt the regime's attack on the city.
"If you decide to leave with dignity... I am personally ready to physically accompany you," said the envoy.
Russia said it was "ready to work" on a French-drafted UN resolution calling for a ceasefire in Aleppo.
More than 300,000 people have been killed since the conflict began with fierce repression of anti-government protests in March 2011.
It has since evolved into a complex multi-front war that has drawn in regional and international forces including, most recently, Turkey.
Ankara launched an offensive on August 24, saying its forces and allied rebels would fight both the Islamic State group and Kurdish militia in northern Syria.
Thursday, at least 29 rebels involved in Ankara's operation were killed in a blast claimed by IS at the Atme border crossing with Turkey, the Observatory said.
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