The main objective of the present study was to develop and characterize naftifine loaded transethosomes and their comparison with marketed cream of naftifine (Exoderil (R), Sandoz Turkiye) for enhanced dermal delivery. Transethosomes loaded with naftifine were developed using the film dispersion method and evaluated for particle size and size distribution, zeta potential, drug recovery yield and stability. The optimal transethosome formulation with a mean particle size of 50.20 +/- 0.22 nm, polydispersity index of 0.056 +/- 0.024 and drug recovery of 96.215 +/- 3.341% was incorporated into hydroxypropyl cellulose, hydroxypropylmethyl cellulose and chitosan gels. The in vitro pig skin penetration of naftifine from transethosome dispersions and transethosomal gel formulations was determined quantitatively by using sequential tape stripping method and compared with the commercial product. The ability of Nile red loaded transethosomes to reach the lower layers of skin was visualized by confocal laser scanning microscopy (CLSM) and ATR-FTIR spectroscopy has been used to study the interaction of transethosomes with the stratum corneum lipids. In conclusion, a topical transethosomal system could be a potential carrier to overcome the stratum corneum barrier and enhance skin penetration and deposition of naftifine.