The aim of this study was to prepare crude extracts from the leaves of Ficus sycomorus (F. sycomorus) native to Oman, and determine their total flavonoids content as well as their antimicrobial activity. Powdered leaf samples were extracted with methanol by using maceration method. The resulting crude extract was suspended in water and successively extracted with hexane, chloroform, ethyl acetate and butanol solvents, respectively. Total flavonoids of the above extracts were determined by the aluminum chloride method, and antimicrobial activity of the same extracts was assessed by a slightly modified disc diffusion method against different Gram (+ and −) bacterial strains. The highest flavonoids content was found in chloroform crude extract followed by that of hexane, butanol, ethyl acetate, and water extracts, respectively. Tested against four bacterial strains, the extracts showed activity in the range of 0–12 mm, using amoxicillin as standard. The present findings could establish this plant as a potential source of antibiotics.