<p>Acrylic dentures are prone to Candida colonization, leading to significant oral health issues such as stomatitis. To combat this challenge, this study developed novel chitosan-cerium oxide (Cs-CeO₂) hybrid nanozymes with inherent antifungal properties for integration into denture materials. The Cs-CeO₂ hybrid nanozymes were synthesized by incorporating cerium oxide nanoparticles into a chitosan matrix, a successful integration confirmed through various physicochemical characterizations. Alongside demonstrating notable antioxidant activity (via DPPH and H₂O₂ assays), the primary objective was to evaluate the antifungal efficacy derived from these hybrid nanozymes. Consequently, acrylic resin composites incorporating the Cs-CeO₂ hybrid nanozymes were fabricated and subjected to comparative analysis of their mechanical properties and antifungal effectiveness against Candida species. The results demonstrated that the acrylic resin embedded with Cs-CeO₂ hybrid nanozymes exhibited significantly enhanced antifungal capabilities, establishing it as a promising candidate for developing infection-resistant acrylic prostheses and preventing oral candidiasis.</p> Graphical Abstract <p>Hybrid Cs-CeO₂ NPs were prepared and identified by various physicochemical methods. Then, the safety of the hybrid Cs-CeO₂ NPs was investigated with a biocompatibility test. Antioxidant activity is also indirectly measured by the effect of antioxidants in controlling oxidation. Therefore, prostheses containing chitosan and the nanoenzyme cerium oxide were prepared and evaluated in an antifungal test and a mechanical test.</p> <p></p>