Santa Margherita di Belice is a town located in the Province of Agrigento within the Italian region of Sicily. It is situated in southwest Sicily at an elevation of approximately 400 metres (1,300 ft) above sea level.
The town lies in the Belice valley among the rivers Belice, Senore, and Carboj. Geographically, it is positioned near the borders where the provinces of Agrigento, Trapani, and Palermo meet. It is located roughly 60 kilometres (37 mi) southwest of Palermo and 60 kilometres (37 mi) northwest of Agrigento.