The aim of this study was to estimate the effect of local and systemic antifungal treatment, accompanied by renewal of complete dentures, on palatal inflammatory papillary hyperplasia (PIPH). The treatment groups consisted of 26 subjects treated with a local antifungal agent (miconazole, 2% gel) for 4 weeks and 13 subjects treated with a systemic antifungal agent (fluconazole, 50 mg) for 2 weeks (test groups). Ten subjects fitted with new complete dentures served as a control group. Variables examined before antifungal and prosthetic treatment included estimation of the size and color of the affected palatal area, measurements of the lengths of the papillae, and salivary variables. Six months after the completion of prosthetic treatment healing was determined as disappearance or marked reduction of the redness of the PIPH. Healing was more often observed in test groups (64%) than in the control group (20%) (p = 0.012). Fifty-eight per cent of the subjects treated with a local (miconazole, 2%) and 77% of those treated with a systemic (fluconazole, 50 mg) antifungal agent were healed. Even though papillary hyperplastic tissue did not disappear, the treatment of PIPH with an antifungal agent without surgery before renewal of dentures might be an alternative treatment in mild cases.