The barrier qualities of the skin are currently the subject of extensive investigation. Despite extensive investigate and progress exertions in this system and the advantages of these technologies, low stratum corneum permeability limits the efficacy of topical drug distribution.. In order to treat systemic and superficial fungal infections, fluconazole, a broad range imidazole derivative, is used. In contrast, the conventional formulation requires a high dose, which may result in serious allergic reactions and irregular heartbeat. Fluconazole niosomes were therefore formulated in an effort to increase lessen the side effects of topical treatment due to the poor skin penetration. The non-ionic surfactants Span 60, Tween 60, and Span 40 were combined with cholesterol in a variety of proportions to formulate fluconazole niosomes through thin film hydration and ether injection. The size, shape, entrapment effectiveness, and in-vitro drug release of the produced niosomal formulations were assessed. The niosomes had a spherical appearance, and their sizes ranged from 3.24 0.11 to 7.38 3.64 m. At the conclusion of 24 hours, it was discovered that the entrapment efficiency ranged from 50.420.51 to 78.630.91% and the in-vitro drug release ranged from 48.540.89 to 76.432.89%. Fluconazole niosomes produced with Span 60 and cholesterol in a ratio of 1:0.2 were the most effective and were added to 1% carbopol gel. The developed gel aimed at a number of physicochemical characteristics, including viscosity, appearance, pH, drug content, and antifungal efficacy. The in-vitro drug release research, which conducted using phosphate buffered saline pH 7.4, revealed a 28.201.73% concentration after 12 hours. This study discovered that the best topical antifungal formulation is fluconazole loaded in niosomes and blended with gel as opposed to generic medication gel.