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Hyperplastic candidiasis (HC) is a chronic infection of oral mucosa caused by Candida. Owing to its potential for malignant transformation, its intervention requires attention. Conventional surgical resection might lead to irreversible damage and impact the patient's quality of life. Hence, this study aimed to evaluate the clinical efficacy of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) alone and in combination with topical antifungal therapy (i.e., nystatin [combination therapy]) in comparison with nystatin and surgical resection for the treatment of HC.Forty subjects with clinical and histopathological diagnoses of HC were included in the study. Four study groups, with 10 participants each, were formed as follows: Group-I - receiving antifungal agent [nystatin]; Group-II - receiving surgical resection; Group-III - receiving PDT; and Group-IV - receiving 5-ALA-mediated PDT and nystatin [combination therapy]. Salivary and mucosal samples were collected for the quantification of Candida albicans and the treatment responses to different interventions were recorded at week-4, week-6, and week-8 after finishing therapies.At the 3The application of 5-ALA-mediated PDT in combination with nystatin gel possesses the potential as a well-tolerated and safe therapeutic modality for the treatment of patients with HC.