This research focuses on deformable liposomes that have great potential as carriers of transdermal drug delivery. In this study, deformable liposomes are prepared using the natural surfactants polyglyceryl‐2 caprate and polyglyceryl‐10 stearate along with phosphatidylcholine and cholesterol to enhance skin penetration of taxifolin and taxifolin tetraoctanoate. Sizes of liposomes made with polyglyceryl‐2 caprate and polyglyceryl‐10 stearate are 64.70–91.30 and 90.20–110.70 nm, respectively. Then entrapment efficiencies and deformability indices are measured, respectively. Liposomes containing 30% surfactant have been selected because they have high entrapment efficiency, stability, and deformability. Crystallization and skin permeation are then measured. Crystallinity is compared using differential scanning calorimetry (DSC). Deformable liposomes containing 30% PGL‐2 caprate and carrying taxifolin tetraoctanoate (CDLTO3) have the lowest melting point (7.55 °C), equivalenting to its highest deformability index. The liposomes are observed by transmission electron microscopy (TEM). Skin permeation studies using Franz cells show that deformable liposomes increased drug permeation more than 1,3‐butylene glycol (1,3‐BG) and control liposomes without surfactant. In particular, when CDLTO3 is used, the amounts of taxifolin tetraoctanoate present in the stratum corneum and skin as well as the amount of permeation are greatest. In conclusion, deformable liposomes containing polyglyceryl‐2 caprate can be effective carriers for taxifolin, taxifolin tetraoctanoate. Practical Applications: Taxifolin is a flavonoid with antioxidative, antibacterial, anti‐inflammatory, and skin‐whitening properties. It would be useful in skin treatments and cosmetics if not for its poor stability. This study develops and characterizes a deformable liposome delivery method that can carry a taxifolin derivative with increased stability and provide better skin penetration compared to conventional liposome. The results can be applied to more effectively deliver beneficial drugs into the skin. Deformable liposomes using the natural surfactants polyglyceryl‐2 caprate and polyglyceryl‐10 stearate increase drug permeation more than did general liposomes. Taxifolin‐tetraoctanoate‐loaded deformable liposomes have the greatest skin permeation.