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Herein we evaluate the effect of nanodiamond (ND) incorporation on the mechanical properties of poly(methyl methacrylate) (PMMA) nanocomposite. Three quantities of ND (0.1, 0.3, and 0.5 wt.%) were tested against the control and zirconium oxide nanoparticles (ZrO). Flexural strength and elastic modulus were measured using a three-point bending test, surface hardness was evaluated using the Vickers hardness test, and surface roughness was evaluated using atomic force microscopy (AFM), while fungal adhesion and viability were studied using Candida albicans. Samples were also analyzed for biofilm thickness and biomass in a saliva-derived biofilm model. All groups of ND-PMMA nanocomposites had significantly greater mean flexural strengths and statistically improved elastic modulus, compared to the control and ZrO groups (P < 0.001). The Vickers hardness values significantly increased compared to the control group (P < 0.001) with 0.3% and 0.5% ND. ND addition also gave significant reduction in fungal adhesion and viability (P < 0.001) compared to the control group. Finally, salivary biofilm formation was markedly reduced compared to the ZrO group. Hence, the incorporation of 0.1–0.5 wt.% ND with auto- polymerized PMMA resin significantly improved the flexural strength, elastic modulus, and surface hardness, and provided considerable fungal resistance.