Denture base poly (methyl methacrylate (PMMA) resin is one of the most frequently used materials in denture base synthesis, but due to its poor mechanical properties, PMMA can be considered a medium for the attachment and growth of a variety of pathogenic bacteria and fungi, particularly due to PMMA's pores and rough surface. The porosity percentage and surface roughness of the PMMA resin sample was lowered in this study, which resulted in a reduction in microorganisms' surface adhesion by varying the ratios of additives such as zinc oxide (ZnO) and tri-calcium phosphate (TCP) nanoparticles with (1, 2, 3, and 10% wt percent) for each additive separately, and 3% as a combination of ZnO and TCP nanoparticles in an equal ratio. Additionally, mechanical features such as surface hardness are developed, which is a critical attribute for polishing and easy finishing, as well as offering great scratch resistance during denture base cleaning. These results indicated that when compared to the other groups, PMMA (ZnO wt. 1%) and TCP-wt. 1%) reinforced composite resins demonstrated the best optimum properties. Additionally, it was discovered that adding 1% of NPs improved the mechanical qualities, which benefited the biological properties by reducing bacterial adherence to the PMMA composite resin.