Abstract: Frog skin histology has been largely explored, particularly in relation to the skin-derived secretions, among which a number of peptides have shown potential medicinal applications. Duttaphrynus melanostictus is a frog species ubiquitous in Indonesia; however, there is only limited information with regard to skin structural characteristics as well as its potential use. The present work explored the structure of the frog skin and further assessed antifungal activity of its extract. Structural studies were carried out by Scanning Electron Microscopic (SEM) assays while antifungal evaluations were performed by testing the activity of the lyophilisate of skin extract against the pathogenic fungi Candida albicans, Microsporum gypseum and Trichophyton mentagrophytes. Results of the structural studies revealed features common to frog species, in particular an extensive distribution of secretory glands. In addition, we observed a flattened, irregular-shaped structure, believed to be secretory ‘vesicle’ of the mucous gland, considered distinct to D. melanostictus. Antifungal studies demonstrated equipotent activity of the lyophilisate against all test fungi. Taken together, results of the present work shed some light on the structural characteristic of D. melanostictus frog skin and further open an opportunity for the development of alternative antifungal agents.