This study investigated the antifungal effects of low-molecular-weight chitosan solution on Candida albicans in denture stomatitis in comparison with nystatin suspension. This randomized, sing-leblind clinical trial included 40 patients diagnosed with denture stomatitis. Patients were divided into two groups, wherein one was treated with chitosan and the other with nystatin for 2 weeks. Changes in the erythematous area were recorded during and after treatment. A palatal smear was obtained for each patient before and after treatment to determine the number of blastospores and mycelia of C. albicans. The results were compared using the Mann-Whitney U test, revealing that the chitosan solution significantly decreased the erythematous surface area, burning sensation, time required for clinical improvement, and number of blastospores and mycelia. The antifungal efficacy of chitosan along with its inherent biocompatibility makes it a promising candidate for use as an antifungal mouthwash.