The objective of this study was to prepare and evaluate itraconazole transdermal gel with different permeation enhancers. Itraconazole transdermal gels were prepared by dispersion method using natural polymer (Tara gum 2% and Kondagogu gum 4%) as gelling agents. Different permeation enhancers such as fatty acids (oleic and stearic), organic acids (citric, acetic, maleic and succinic), sulfoxides (dimethyl sulfoxide) with 2 different concentrations 1% and 2.5% were used. The prepared gels were evaluated for physicochemical properties, in vitro, ex vivo, skin irritation and stability studies. All formulations have shown good physicochemical properties. In vitro diffusion studies concluded that ITC1, ITM1, ITSU1, IKC1, IKM1 and IKSU1 have shown more than 90% drug release for 4-7 h. Ex vivo permeation studies of the ITM1 has shown better release of itraconazole in 8 h with Q8 of 2319.109 ± 5.91 μg/cm2; flux of 281.12 ± 0.98 μg/cm2/h; permeability coefficient of 110.199 ± 0.98 cm/h × 10-3 and enhancement ratio of 6.428 ± 0.12. Skin irritations studies have shown ITM1 to be non-irritant. ITM1 formulation was found to be stable for one month at room temperature. Based on results, it can be concluded that ITM1 formulation with maleic acid (1%) as permeation enhancer can provide good permeation of itraconazole for the treatment of basal cell carcinoma.