The present investigation was undertaken to find out the phytochemical profile of aqueous, ethanolic, methanolic, butanolic and acetone extract from the leaves of Piper betle and to determine in vitro antimicrobial activity of Piper betle leaves against various microorganisms. The phytochemical screening reveals that, the aqueous, ethanolic and butanolic extracts contains valuable phytochemicals like steroids, diterpenes, tannin, flavonoids etc. and found rich in phytochemicals. Comparatively the aqueous extract yields more secondary metabolites qualitatively and quantitatively among all. The butanolic extracts shown higher inhibition zone against all the bacteria except the fungus and found more effective and efficient among the extracts prepared in various solvent systems although aqueous extract yielded more phytochemicals. All the extracts were fails to show zone of inhibition against A. niger. Thus, these results confirms the presence of active antibacterial compounds in the leaves of Piper betle, might be used as a source of antibiotics for the treatment of various respiratory diseases and the diseases caused by various bacteria.