Crude methanolic and hexane extracts of seeds of citrullus colocynthis were examined for antimicrobial effects of different concentrations ranging from (3.1- 50) mg/ml against Staphylococcus aureus, Streptococcus pyogenes, Listeria monocytogenes, Bacillus subtilis, Proteus vulgaris, Escherichia coli, Klebsiella pneumoniae, Psendomonas aeruginosa, Salmonella typhi, Entero coccus spp. and Candida albicans. The agar well diffusion methode was used in this study.The extract was found to be active against S.aureus, B.subtilis, P. vulgaris, K. pneumoniae, and PS. aeruginosa at concentrations of (50, 25, 12.5, 6.25) mg/ml.while S. pyogenes and L.monocytogenes were sensitie at (50, 25, 12.5) mg/ml. E. coli shown sensitivity at (50, 25)mg/ml. Enterococcus spp. and Salmonella typhi showed no response. Candida albicans was sensitive to all different concentrations. Hexane extract was less effective against the tested microorganisms than methanolic extract. The results support the notion that Citrullus colocynthis seeds extract may have a role in pharmacentical uses, like antimicrobial drugs.