Government forces seized Kafr Batna and Sabqa in the south of the enclave, the Britain-based Syrian Observatory for Human Rights said, as thousands of civilians fled into regime-held territory.
Russia-backed regime forces have retaken more than 80 percent of the last opposition bastion outside the capital since launching a blistering air and ground offensive on February 18, the Observatory says.
The assault has split opposition-held areas into three shrinking pockets each held by different rebels.
The southern pocket is held by the Faylaq al-Rahman rebel group, which the Observatory says counts some 8,000 fighters in its ranks.
After Saturday's advance, the group now controls just a handful of areas, the monitor says: Arbin -- the largest -- as well as Zamalka, Hazeh, Ain Tarma and parts of the Damascus neighbourhood of Jobar.
Thousands of civilians streaming out of the enclave into regime-held areas on Saturday came mostly from this southern sector, it said.
On Friday, the enclave's main rebel groups -- Faylaq al-Rahman, Jaish al-Islam and Ahrar al-Sham -- said they would be willing to hold direct UN-sponsored talks with regime backer Russia on a ceasefire.
More than 1,400 civilians have been killed since the regime offensive began, the Observatory says, while tens of thousands more have fled.
Jaish al-Islam controls an area around the main town of Douma in the north of the former enclave, while Ahrar al-Sham holds influence in the area of the town of Harasta to the west.