Cenchrus setigerus (Poaceae) is most suitable and highly nutritive grass for desert environmental conditions. This grass, fed green, turned into silage, or made into hay is said to increase flow of milk in cattle and impart a sleek and glossy appearance. Seeds of this grass are used as famine food by the tribal during severe conditions. However, estimation of antimicrobial activities and identification of any bio-active compound still not have been done in this grass. Aim of the study was to determine the possible bioactive components of C. setigerus and antimicrobial activity in various polar solvents from the leaves of the plant. The prevailing compounds in the ethyl acetate extract of C. setigerus were 4,22-stigmastadiene-3-one (4.14 %), ergost-5-en-3-ol (campesterol) (1.94 %), cyclopentacycloheptene (azulene) (0.99 %) and myristic acid, isopropyl ester (0.15 %) and the highest antimicrobial activity was exhibited by the glacial acetic acid extract against P. merabilis. The presence of various bioactive compounds justifies the use of this plant for various ailments by traditional practitioners. However, isolation of individual photochemical constituents and subjecting it to biological activity will definitely give more fruitful results.