Paclitaxel is a current standard chemotherapeutic drug for ovarian cancer with several side effects. Recurrences of drug resistant clones have been considered the serious problem in the failure of chemotherapy. Medicinal marine natural products have been intensively proposed as diverse chemotherapeutic agents. Therefore there is an affinity to find efficient modality to overwhelm ovarian cancer chemo resistance complication. Here we examine whether brittle star extract as marine echinoderm natural resources can remarkably improve the cytotoxicity of paclitaxel in human ovarian cancer. MTT (dimethyl thiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay, PI (Propodium Iodide) assay, DAPI (4', 6-diamidino-2-phenylindole) staining, Acridine orange staining, caspase-3 and caspase-9 were performed to investigate cytotoxic effect. We found that a combination of sub-toxic concentrations of brittle star methanolic extract (lower than IC50) can significantly enhance ovarian cell growth inhibition and intrinsic apoptosis pathways induced by paclitaxel. Consequently a combination of paclitaxel and brittle star extract may offer novel innovative strategies for ovarian cancer chemotherapy.