Anti-microbial activity of root, stem and leaf extracts of Phyllanthus amarus were studied with polar solvents such as ethyl acetate, dimethyl Formamide and non-polar solvents such as chloroform, dichloromethane and n-Hexane extracts against Gram positive bacteria viz. Bacillus cereus ,Bacillus subtilis and Gram negative bacteria viz. Pseudomonas aeruginosa,, Escherichia coli, Klebsiella pneumoniae using Agar well diffusion method. Root, stem and leaf extracts of Phyllanthus amarus were evaluated separately to determine the best explant source for potential antimicrobial effect. Amikacin and Nitrofurantoin were used as positive control. Leaf extracts in dimethyl formamide and dichloromethane exhibited better antimicrobial activity compared to root and stem extracts. The extracts were further subjected to GC-MS analysis for identification of compounds responsible for anti-microbial activity. MIC and MBC studies were carried out by macro-dilution method. The assessment of anti-microbial activity of this plant helps in correlating the ancient and modern way of disease treatment for large scale testing of novel pharmacopeia.