Mukia maderaspatana (L.) M. Romer., is an annual monoecious tendril climber, belonging to the family Cucurbitaceae, mostly prevalent in South India. It is commonly called Musumusukkai in Tamil. It is a traditional medicinal plant used for a considerable time in Siddha for treatment of various diseases The ethanol extract of leaf and root part of the plant were tested for their antimicrobial activity using well diffusion assay method against common human pathogens, Escherichia coli, Streptococcus pyogenes, Helicobacter pylori, Pseudomonas aeruginosa, Aspergillus niger, Candida albicans, Trichoderma viride and Fussarium spp. Both the leaf and root extracts shows antimicrobial activity in concentration dependent manner. Leaf extract shows broad spectrum of antimicrobial activity in tested organism than root.