The ocotillol (OCT)-type saponins have been known as a tetracyclic triterpinoid, possessing five or six-membered epoxy ring in the side chain. Interestingly, this type saponin was mostly in Panax vietnamesis Ha et Grushv., Araliaceae (VG), hence making VG unique from the other Panax spp. Five OCT-type saponins, majonoside R2 ( 1 ), vina-ginsenoside R2 ( 2 ), majonoside R1 ( 3 ), pseuoginsenoside RT4 ( 4 ), vina-ginsenoside R11 ( 5 ), together with three protopanaxadiol (PPD)-type saponins 6-8 and four protopanaxatriol (PPT)-type saponins 9-12 from VG were evaluated for their anti-melanogenic activity. All of isolates were found to be active. More importantly, 1-5 inhibited melanin production in B16-F10 mouse melanoma cells, without showing any cytotoxicity. Beside ginsenoside Rd (6) and ginsenoside Rg3 (8) in PPD and notoginsenoside R1 (12) in PPT-type saponins, 1 was the most potent melanogenesis inhibitory activity. In this paper, we highlighted anti-melanogenic activity of OCT-type saponins and potential structure-activity relationship (SAR) of ginsenosides. Our results suggested that OCT-type saponins could be used as a depigmentation agent.© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.