Oral candidiasis leading to denture stomatitis is a fungal infection resulting from unregulated growth and adhesion mainly of Candida albicans onto acrylic denture base. Once the biofilm is formed, it is immune resistant and mainstay treatments involve toxic chemical antifungal agents or mechanical cleaning techniques, both offer limited efficacy. Consequently, there is an urgent need for more effective and safer therapeutic approaches. While biological modalities are expanding in general medicine, the exploration of protein-based therapeutics in dental medicine remains limited. This research evaluates the inhibitory effect of recombinantly expressed psoriasin on the growth of Candida albicans on polymethyl methacrylate denture bases. Psoriasin, also known as S100-A7, has shown promise in treating microbial skin infections, and its natural presence in saliva makes it a promising candidate for treating oral microbial infections. Our findings indicate that psoriasin exhibits a strong, dose-dependent inhibition of Candida albicans growth. Further, we incubated a polymethyl methacrylate denture base within the psoriasin solution. Notably, immersing the denture base in the solution completely eradicated fungal growth. Our research utilizes natural antifungal proteins within biomedical devices like denture bases, suggesting psoriasin as a safe alternative to chemical antifungals in dental medicine.