Background:: Candida albicans is the yeast that causes the fungal infection known as candidiasis. One of the standard methods for treating candida is the application of fluconazole. The low solubility of fluconazole in aqueous media is a big problem in the use of this agent. Novel drug delivery systems, such as microemulsions, could be applied to solve this problem. The main aim of this study was to perform statistical optimization of the formulation and physicochemical characterization of fluconazole microemulsion. Methods:: Optimization of the microemulsion formulation was done by using experimental design software, and then fluconazole was loaded onto the best formulation at a concentration of 1 % w/w. The physiochemistry of the microemulsion formulation was assessed by pH measurement, rheology measurement, simultaneous thermal analysis, and Scanning Electron Microscopy (SEM). Results:: The two-level fractional factorial design application demonstrated the optimum formulation to consist of surfactant, co-surfactant, oil content, and water, comprising 58%, 27%, 10%, and 5% of the formulation, respectively. Desirable thermal mass was observed up to 150°C. The formulation was a non-Newtonian shear-thinning liquid in terms of viscosity, with a reported pH between 6.5-7. Conclusion:: Considerably stable, high-quality microemulsion formulations containing fluconazole are presented, which are applicable for antifungal skin candidiasis treatment in clinical trials.