Candida albicans is a common fungal pathogen that causes systemic and superficial infections in most immunocompromised patients. Fluconazole, a synthetic triazole antifungal agent, is the most prescribed drug used in treating this pathogen. But because of its poor solubilization in water and the emergence of resistant strains against this antimycotic drug, we aimed at devising a unique microemulsion drug delivery system for fluconazole against candidiasis. A clear oil-in-water microemulsion system, consisting of clove oil as oil phase, Tween 20 as surfactant, and water as aqueous phase was developed using a ternary phase diagram. Physicochemical characterization was done to understand the internal physicochemical state. The bulk drug, fluconazole, that measured several microns in length was reduced to a 10-65 nm range with no means of high-energy methods as confirmed by transmission electron microscopy. The very small and uniform spherical structure of the drug-loaded microemulsion system could be of high impact to the biological system as the efficacy of fluconazole is greatly improved when compared with its conventional bulk form. The optimized microemulsion exhibited significantly higher antifungal activity at a minimum concentration (8 μg/ml) of fluconazole as examined by fluorescence and scanning electron microscopy. Thus, our report discloses an excellent oral drug delivery system. © 2013 International Union of Biochemistry and Molecular Biology, Inc.