Curcumin is a novel phytochemical compound proven to be effective in treating many types of cancers, including skin cancer. But its therapeutic applications are limited due to its poor aqueous solubility, stability, and permeability. Methods: To overcome these problems, a novel non-aqueous gel formulation loaded with curcumin was developed for topical administration, using Versagel as the gel base, and its ex vivo permeability characteristics were evaluated. Results: The formulations showed a good spreadability, with 18.6% and 23-40% of the drug released within 24 hours of ex vivo studies. The drug release data were fitted to the Higuchi model and the Korsmeyer-Peppas model. The rate of drug release followed first-order kinetics, and the mechanism of drug release was found to be pure Fickian diffusion. Stability studies revealed that curcumin was stable at room temperature, with a calculated half-life of 1506 days. No skin irritation was observed in the skin irritation test. Conclusion: It is concluded that for drugs unstable in aqueous physiological environments, with poor permeability and oral bioavailability, incorporating them into a non-aqueous topical gel (Versagel) represents a novel approach to enhance their stability and therapeutic efficacy in skin cancers.