The Syzygium calophyllifolium is a large evergreen tree growing in higher altitude in Southern Western Ghats, India. The ethyl acetate extract of leaves contain higher proportions of sesquiterpenoids and triterpenoid compounds that showed effective antimicrobial screening against some of bacterial and fungal strains. The extract showed maximum inhibition zones against Enterococcus faecalis and Trichophyton mentagrophytes. The extract also showed notable antioxidant activity and at higher concentration scavenged 81.45 % of free radicals. A potent cytotoxicity has been exhibited by the extract, showing increased activity with increasing concentration. The study suggests that leaves of Syzygium calophyllifolium may be a prominent source of several medicinally important natural compounds.