Phytochemical are extensively found at different levels in many medicinal plants. The aim of the present study was to evaluate the antimicrobial activity of Azadirachta indica and Cyperus rotundus against Staphylococcus aureus, Streptococcus faecalis, Bacillus subtilis and Escherichia coli. Plant samples were collected from Virudhunagar and Ramanathapuram Districts, Tamil Nadu. Crude extracts of the dried samples were made using solvents such as butanol, ethanol, methanol, chloroform, propanol, hexane, diethyl ether and aqueous. The antimicrobial activities of plant extracts were determined by agar well diffusion method and zone of inhibition was measured. Butanol extract of Azadirachta indica resulted maximum zone of inhibition against E.coli, S.aureus, and S.faecalis. in case of Cyperus rotundus ethanol extract against E,coli, butanol extract against B.subtils, methanol extract against S.aureus and butanol extract against Streptococcus results maximum zone of inhibition. Further investigation with the pure compound is required to check the accuracy of the activity which is responsible for the inhibition.