Background: Cerium oxide and chitosan (Ce/CS) nanoparticles have garnered significant interest due to their remarkable properties, including antioxidant activity, biocompatibility, antibacterial effectiveness and antiinflammatory activities. This study evaluates the impact of incorporating a Ce/CS nanocomposite into polymethylmethacrylate (PMMA) resin on its mechanical properties. The composite consisted of 30% cerium oxide and 70% chitosan by weight (wt), with varying percentages incorporated into the PMMA resin selected according to a pilot study. Material and Methods: Ninety PMMA specimens were fabricated and categorized into three groups according to the Ce/CS nanocomposite percentage in the PMMA resin: control (0 wt%), group A (1 wt%), and group B (5 wt%). Transverse strength, impact strength, and surface hardness were assessed, with 10 specimens for each test. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) were used to examine the chemical and surface alterations of PMMA resin. The collected data were analyzed using one-way ANOVA and Tukey HSD test, with a significance level of P≤0.05. Results: The resulting data revealed a significant difference among all groups (P≤0.05). Group A exhibited the highest values in transverse and impact strength compared with the other groups. Group B showed the highest values in surface hardness compared with group A and the control group. The FTIR graph indicated changes in the material's chemical structure, suggesting the formation of new functional groups. SEM image showed an even distribution of Ce/CS nanocomposite inside the PMMA matrix of group A compared with group B. Conclusion: The study concludes that incorporating 1 wt% of a nano cerium oxide/chitosan composite into PMMA denture base resin significantly enhances its transverse and impact strength compared with 5 wt%. Furthermore, both 1 wt% and 5 wt% Ce/CS nanocomposites resulted in a notable improvement in the surface hardness of the PMMA resin.