De Mistura, who is joined by Deputy Envoy Ramzy Ezzedine Ramzy, is expected to meet with Syrian President Bashar al-Assad on Wednesday, where he will likely advocate a strategy for reducing conflict between the regime and rebels through local cease-fire agreements.
According to the U.N. humanitarian coordinator in Syria, Yacoub El Hillo, there are an estimated 40 truces currently being negotiated.
Negotiated cease-fires between the regime and rebels would not only curtail the devastating effect of the three-year-old civil war, which has displaced more than three million Syrians, but could also help contain Islamist extremists in Syria, who are considered a threat to both the regime and rebels.
De Mistura's meeting comes ahead of President Barack Obama's Wednesday evening speech, during which he will unveil his strategy "to degrade and ultimately destroy ISIL."
U.N. Secretary-General Ban Ki-moon appointed de Mistura in July to replace Algerian diplomat and former U.N.-Arab League Joint Special Representative Lakhdar Brahimi, who resigned in May. Mistura served previously as a U.N. envoy for the conflicts in Afghanistan and Iraq.