To develop a more effective transdermal delivery method for lipophilic functional cosmetic compounds such as retinol, we formulated various deformable liposomes and compared their transdermal delivery efficiency with those of neutral or negatively-charged conventional liposomes. We tested the deformability of liposomes containing edge activators such as bile salts, polyoxyethylene esters and polyoxyethylene ethers. As indicators of deformability, we used the passed volume and phospholipid ratios during extrusion, as well as the deformability index. We found that the type of edge activator significantly affected the extent of deformability, and that Tween 20 provided the highest level of deformability. Accordingly, we used Tween 20 to formulate deformable liposomes containing retinol in the membrane bilayers, and conducted a skin permeation study in Franz diffusion cells, using dermatomed human skin and three-dimensional human keratinocyte layers. As compared with the use of conventional neutral or negatively-charged liposomes, the use of Tween 20-based deformable liposomes significantly increased the skin permeation of retinol. These results suggested that deformable liposomes might be of potential use for the formulation of retinol and other lipophilic functional cosmetic compounds.