Polymethyl methacrylate (PMMA) possesses favorable properties such as a valuable physical characteristic, low cost, and its ease and aesthetic fabrication. However, it suffers from low hardness and tribological properties in denture base applications. In this work, the mechanical and tribological properties of PMMA reinforced with organic, inorganic, and hybrid of organic/inorganic nanoparticles (NPs) were investigated. The used organic fillers were date seed (DS) NPs and inorganic fillers were titanium dioxide ( TiO2) NPs. TiO2 and DS NPs were characterized by transmission electron microscope (TEM). PMMA-based non-hybrid and hybrid nanocomposites were fabricated by using a self-curing method. To fabricate the nonhybrid composites of C1 and C2, TiO2 and DS NPs were added at a constant weight fraction (wt. %) of 1.2 to PMMA, respectively. For manufacturing hybrid nanocomposites, C1 was reinforced by 0.1, 0.2, 0.3, 0.4, and 0.5 wt. % DS NPs. Also, C2 was reinforced with TiO2 NPs at the same loading content of 0.1, 0.2, 0.3, 0.4, and 0.5 wt. %. Unfilled PMMA, C1, C2, C1/0.4 wt. % DS NPs, and C2/0.4 wt. % TiO2 NPs were analyzed by Fourier transform infrared (FTIR) technique. Vickers hardness number (VHN), wear rate, and coefficient of friction (COF) tests were conducted to study the effect of hybrid NPs content on the mechanical and tribological properties of PMMA. The worn surfaces of rubbed specimens after the wear test were imaged by scanning electron microscope (SEM). nanocomposites of C2/0.4 wt. % TiO2 NPs is lower than that of the hybrid nanocomposites of C1/0.4 wt. % DS NPs by 47.61%.