The therapeutic efficacy of tea tree oil (TTO), Melaleuca alternifolia, and its main component, terpinen-4-ol, were evaluated in a murine oral candidiasis model. Prednisolone -pretreated mice were orally infected with a fluconazole-susceptible (TIMM 2640) or a resistant (TIMM 3163) strain of Candida albicans to induce oral candidiasis. TTO or terpinen-4-ol was administrated with a cotton swab 3 h and 24 h after candida infection. These treatments clearly showed a decrease in the symptom score of tongues and in the viable candida cell number in the oral cavity at 2 d after azole-susceptible C. albicans infection, although the degree of the efficacy was less than that of fluconazole. Even against oral candidiasis caused by azole-resistant C. albicans, TTO and terpinen-4-ol were similarly effective, while fluconazole appeared ineffective. These results suggest that TTO and terpinen-4-ol may have the potential of therapeutic ability for mucosal candidiasis which may also be applicable to C. albicans oral candidiasis induced by the azole-resistant strain.