At least 200 people were injured, with the death toll – most of them civilians – likely to rise as many of the wounded were in serious condition, the Syrian Observatory for Human Rights said.
"The regime carried out four air strikes against a market in the centre of Douma," said Observatory director Rami Abdel Rahman.
"The preliminary information suggests most of the dead are civilians," he added.
Read: More than 230,000 killed in Syria conflict: monitor
Abdel Rahman said locals had gathered at the site after the first strike to help evacuate the wounded when more raids struck.
The devastating attack on Douma came as UN humanitarian chief Stephen O'Brien made his first trip to Syria since taking the top aid post in May.
A video posted online by activists of the aftermath of the attacks showed an intersection strewn with rubble and twisted metal.
Several buildings appeared to have their fronts almost sheared off by the force of the blasts, and many vehicles were overturned and crumpled amid the rubble.
Read: Syria regime barrel bombs kill 24, including children: monitor
Douma lies in the rebel bastion of Eastern Ghouta, a region outside the capital that is a regular target of government air strikes.
Earlier this week, Amnesty International accused the government of war crimes in Eastern Ghouta, saying heavy aerial bombardment was compounding misery created by a regime blockade on the area.
Rebels also regularly fire on the capital from the region, attacks that Amnesty also described as war crimes because of their indiscriminate nature.
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