This study was conducted to examine the activity of alpha-mangostin against Candida albicans, the most important microorganism implicated in oral candidiasis. Its activity was compared to Clotrimazole and Nystatin. Results showed that alpha-mangostin was effective against C. albicans, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were 1,000 and 2,000 μg/ml, respectively. The C. albicans killing activity of alpha-mangostin was more effective than Clotrimazole and Nystatin. The cytotoxicity of alpha-mangostin was determined and it was found that alpha-mangostin at 4,000 μg/ml was not toxic to human gingival fibroblast for 480 min. The strong antifungal activity and low toxicity of alpha-mangostin make it a promising agent for treatment of oral candidiasis. (J Oral Sci 51, 401-406, 2009)