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Background: The study aimed to compare the antimicrobial activity and cytotoxicity of saponin extracted from six sea-cucumber species, licorice, and ginseng to determine the most potent one. Methods: Antimicrobial activity assessed by well diffusion and agar dilution methods. The inhibitory effects of the tested extracts on cell growth of Liver (HePG-2) and breast (MCF-7) cell lines assessed by MTT [3- (4, 5- dimethyl thiazol-2yl) - 2, 5- diphenyl tetrazolium bromide] assay. Results: The results revealed that licorice extract presented higher antibacterial activity against Gram-positive bacterial strains than sea-cucumber extracts; but has comparable results for Gramnegative (Salmonella tyhimurium, Klebsiella spp, and Acinetobacter baumanii). Holothuria atra body wall and Bohadschia tubules have the highest antifungal effect against Candida albicans, Candida krusei, Candida famata, Candida glabrata, and Candida tropicalis. Sea-cucumbers are more potent against fungal strains than licorice and ginseng extract. Licorice and ginseng presented higher cytotoxicity against HePG2 and MCF-7 cell lines than sea-cucumbers. Conclusion: This study promotes the use of licorice extract as a better antibacterial substance than sea-cucumber extracts; however, the use of sea-cucumber extracts as antifungal agents than herbal extracts. Also, we support the utilization of licorice and ginseng as a cytotoxic agent instead of seacucumbers to stop the fishing of animals and consequently save it from extinction.