north american birch species of the boreal forest contain significant amounts of pentacyclic triterpenes in their outer bark. betulin (be) and betulinic acid (ba), pentacyclic triterpenes readily extracted from outer birch bark, have been reported to exhibit a wide array of therapeutic effects, including selective inhibition against melanoma, and the inhibition of key enzymes involved in skin aging and melanogenesis. despite their promising therapeutic effects and lack of toxicity towards healthy cells, their use in pharmaceuticals and cosmetics has been limited by their poor hydrosolubility. ethosomes are lipid vesicles that have been successfully employed to encapsulate hydrophobic compounds and enhance their drug delivery and bioavailability. the aim of this study was to investigate the use of ethosomes as a delivery system for triterpenes and evaluate their anti-melanoma and anti-melanogenic effects. be, ba, and a triterpene extract from betula papyrifera (te) were successfully incorporated into an ethosome for the first time and assessed for their anti-melanoma and anti-melanogenic effects in b16-f10 melanoma cells. firstly, ethosomes containing be, ba, or te were prepared and characterized by their vesicle size, entrapment efficiency, and morphology. the cytotoxicity on b16-f10 melanoma cells was then explored. lastly, the effect on cellular tyrosinase activity in b16-f10 cells was evaluated as a measure of anti-melanogenic effect. the ethosomal triterpenes had mean vesicle sizes ranging from 3.67 – 5.11 μm and high entrapment efficiencies ranging from 93.25 – 95.76%. the ethosomal triterpenes showed significant cytotoxicity and higher in vitro anti-melanoma effects than triterpene solutions of equivalent concentration. be-ethosomes showed an ic50 of 2.43 μm compared to 14.38 μm in be solutions. ba-ethosomes showed an ic50 value of 3.07 μm compared to 16.41 μm in ba solutions. te (ic50 = 36.00 μg/ml) showed cytotoxicity comparable to both be and ba, but its effect was not improved by the ethosomal solution (ic50 = 43.51 μg/ml). be, ba, and te showed significant anti-melanogenic effect, inhibiting tyrosinase more effectively than the standard inhibitor kojic acid. these findings support the use of be, ba, and te as therapeutic agents and outlines their potential for topical and transdermal applications for the treatment of melanomas and skin aging.