The agar diffusion method was used to determine the antimicrobial activities of Euphorbia hirta (EH) and  Polygonum plebeium (PP) against S.aureus ,B39.Ethyl acetate extract of Euphorbia hirta  (EH) and Polygonum plebejum (PP),was the most effective solvent. MIC of plant extract Polygonum plebeium (PP) and Euphorbia hirta (EH) was 25mg/ ml. The antimicrobial activity of ethyl acetate extract of E. hirta (EH) and P. plebeium (PP)  was more effective when incubated at 25°C for 10 min with MRSA, B39; pH 5 was more effective against MRSA, B39. Light condition for 24hr was effective against MRSA, B39; Static condition had slight effectiveness against MRSA, B39.  Xylose  exhibited the highest activity on MRSA, B39; no amino acids, metallic ions and vitamins  were effective.  Ethyl acetate extract of  E. hirta (EH) was subjected to column chromatography and monitored with TLC, 5 spots were detected. Anti MRSA spots were identified as Hydroquinone and O-coumaric acid.