Holothurians antifungal and antibacterial activity to human pathogens in the Persian Gulf. Pharmaceutical industries now accept that oceans contain a vast array of organisms with unique biological properties. As investigation of antimicrobial activity, three species of Holothuria sea cucumbers (Holothuria scabra, Holothuria parva and Holothuria leucospilota) from the Persian Gulf, Iran, were obtained, their different organs: gonads (G), body wall (BW), intestine tract (IT), respiratory tree (RT) were isolated and extracted with organic solvents: ethyl acetate and methanol. Antifungal and antibacterial activities of each fraction was estimated with a minimum inhibitory concentration (MIC) and disk-diffusion method against the number (i.e. n=10) of human pathogenic microbes (eight pathogenic Gram-positive/negative bacteria strains and two fungi). All the sea cucumbers extracts confirmed their strong potential antagonistic effect against the bacterial and fungal indicators, except for three relatively resistant microbial strains: Candida albicans and Pseudomonas aeruginosa and Klebsiella pneumonia. Most effective antifungal and antibacterial activities were recorded for methanolic extract of intestine tract organs of H. parva against Saccharomyces cerevisiae (MIC=0.09mg/ml, IZ=22±0.8mm) and Staphylococcus epidermidis (MIC=0.04mg/ml and IZ=30±0.9mm), compared the other extracts. Nevertheless, the differences between species can result from a variety of their natural habits. The finding suggests that marine Holothuria sea cucumber specie, especially H. parva, has a potential source for the discovery of natural antibiotic compounds and drug development.