In the present investigation antimicrobial activity of leaf extracts and various column eluted fractions of the medicinal plants Andrographis paniculata and Melia azadirach L. were evaluated against the clinical bacterial strains viz. Pseudomonas fluorescence, Vibrio cholerae, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Staphylococcus aureus and the fungal strains viz., Trichophyton rubrum, Aspergillus niger, Aspergillus fumigatus and candida albicans. The antimicrobial activity was carried out by agar disc diffusion and well cut methods. The methanol extracts of Andrographis paniculata and Melia azadirach L were found with potential antimicrobial activity against Pseudomonas aueruginosa (22mm), Staphylococcus aureus (21mm) and moderate activity was recorded against Vibrio cholerae (14mm).