Walid Muallem said Damascus could not agree to the idea floated by the UN's peace envoy Staffan de Mistura, who held talks in Syria on Sunday aimed at reducing violence in second city Aleppo.
"He talked about an autonomous administration" in east Aleppo, Muallem said after meeting with de Mistura.
"We told him that we reject that completely."
"How is it possible that the UN wants to reward terrorists?" he asked.
Syria's government refers to all those opposed to President Bashar al-Assad's regime as "terrorists".
De Mistura's visit comes as the Syrian government presses a fierce assault on the rebel-held east of Aleppo, which has been besieged by regime troops since mid-July.
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The UN envoy recently floated a proposal to halt fighting in the city, under which jihadist forces would leave and the government would recognise the opposition administration in the east of the city.
"We told him that we agreed on the necessity of terrorists leaving east Aleppo... but it is not possible that 275,000 of our citizens... are kept hostage by 5,000, 6,000, 7,000 armed men," Muallem added.
"There is no government in the world that would accept that," he said.
"The sooner they leave -- and we have allowed them to choose where they want to go -- the sooner they will spare the suffering of the residents," he said.
"The institutions of state must return to east Aleppo."
Muallem said de Mistura had not suggested a new date for peace talks to resolve Syria's conflict, which has killed more than 300,000 people since it began in March 2011, with anti-government protests.
Several rounds of internationally sponsored dialogue sessions and peace talks have already failed to move the government and rebels closer to a peaceful resolution of the conflict.
De Mistura was holding additional meetings and said he expected to issue a statement later Sunday.