Herbal compounds have different physicochemical properties. Its use on the oral route often has low biological availability. Therefore, alternative transdermal routes are used through the skin. The stratum corneum skin layer is the most difficult layer to penetrate. Therefore it is necessary to use a drug delivery system such as ethosomes, transfersome or transethosomes to increase transdermal drug delivery. Ultradeformable vesicles (UDV) have recently become a promising tool for the development of improved and innovative dermal and transdermal therapies. The aim of this investigation was to formulate, evaluate and compare the transdermal potential and psoriasis activity of novel vesicular carriers: transethosomes and ethosomes of Nigella sativa. Transethosomes (Te) and ethosomes (E) were prepared by thin-layer hydration and cold method respectively and were characterized for zeta potential (ZP), vesicle size and polydispersity index, shape and surface morphology and entrapment efficiency. Optimized Te and E formulation was incorporated into gels was characterized by viscosity, pH measurement, spreading diameter, in vitro release studies, permeation data analysis, drug content, fluorescence microscopy.Transethosomal and ethosomal formulation showed particle size of 172±11nm and188±11nm. Transethosomes showed drug entrapment (71.7±2.7%) than ethosomes (78.6±3.1%). Both the formulation showed good zeta potential indicating good stability.Drug content of transethosomal and ethosomal gel formulation was found to be 74.1±1.9 and 70.5±2.1 respectively. In vitro drug release through animal skin of transethosomes and ethosomes gel was found to be 98.23% and 95.65% respectively. The prepared transethosomes gel of N. Sativa extract loaded was found to be more effective in imiquimod-induced psoriasis; DNCB induced dermatitis and in inflammation as compared to Nigella sativa extract loaded ethosomal gel. This may be due to the fact that incorporation of phytoconstituents into vesicular system like transethosomes resulted in much better absorption profile which enables them to cross the biological membrane, resulting in enhanced bioavailability. The therapeutic action becomes enhanced, more detectable, and prolonged. Hence, the results suggested transethosomes to be a more efficient carrier system as compared to ethosomes for transdermal delivery of Nigella sativa