Calotropis procera (Ait) R. Br. is evergreen small woody shrub growing wildly in many parts of the world especially warm places. Its leaves have significant bilirubin lowering, antioxidant, antiplasmodial, anti-inflammatory, wound healing properties and are used to treat body pain, burns, injuries, rheumatism, sinus fistula and snake bite. GC-MS analysis of ethanolic extract of the leaves showed the presence of triterpenes (16.62%) including norolean-12-ene (2.11%), methyl commate A (4.23%), 9,19-cyclolanost-24-en-3β-ol (1.31%), lup-20(29)-en-3-olβ acetate (2.43%) and lupeol (1.64%) and steroids (14.07%) viz., cholesta-4,6-dien-3β-ol benzoate (1.14%), (24R)-ergost-5-en-3β-ol (3.75%), stigmast-5-en-3β-ol (3.56%) and stigmasta-5,24(28)-dien-3β-ol (1.31%).The other compounds detected in the leaf extract were alkanes (4.53%), aliphatic amides (2.59%), fatty esters (1.84%), oxo-alkane (1.06%), diterpene alcohol, (1.07%) and acyclic diterpene (1%) were also present. The leaf ethanolic extract showed significant antimicrobial activity against Escherichia coli and Staphylococcus aureus in all concentrations. Mild antibacterial activity was observed with Bacillus subtilis and Streptococcus pyogenes in high concentrations. Futher the isolation, chemical characterization and clinical activities of the major chemical constituents of the leaves can be carried out.