Denture stomatitis presents as a chronic disease in denture-bearing patients, especially under maxillary prosthesis. Despite the existence of a great number of antifungal agents, treatment failure is observed frequently. Propolis, a natural bee product, possesses well-documented antifungal and anti-inflammatory activities. The purpose of this study was to evaluate the clinical efficacy of a new Brazilian propolis gel formulation in patients diagnosed with denture stomatitis. Thirty complete-denture wearers with denture stomatitis were enrolled in this pilot study. At baseline, clinical evaluation was performed by a single clinician and instructions for denture hygiene were provided. Fifteen patients received Daktarin (Miconazole gel) and 15 received Brazilian propolis gel. All patients were recommended to apply the product four times a day during one week. Clinical evaluation was repeated by the same clinician after treatment. All patients treated with Brazilian propolis gel and Daktarin had complete clinical remission of palatal edema and erythema. This new Brazilian propolis gel formulation had efficacy comparable to Daktarin and could be an alternative topical choice for the treatment of denture stomatitis.