The study evaluates the effect of adding graphene-Ag nanoparticles (G-AgNp) to a PMMA auto-polymerizing resin, with focus on antibacterial activity, cytotoxicity, monomer release, and mechanical properties. Auto-polymerizing acrylic resin (M) was loaded with 1 wt% G-AgNp (P1) and 2 wt% G-AgNp (P2). Methyl methacrylate monomer release (MMA) was measured after immersion of the samples in chloroform and cell medium respectively. Cell viability was assessed on dysplastic oral keratinocytes (DOK) and dental pulp stem cells. Oxidative stress and inflammatory response following exposure of dysplastic oral keratinocytes to the experimental resins was evaluated. Antibacterial activity against Staphylococcus aureus, Streptococcus mutans and Escherichia coli and also flexural strength of the resins were assessed. Residual monomer: For samples immersed in chloroform, MMA concentration reached high levels, 10.27 μg/g for sample P1; MMA increased at higher G-AgNp loading; 0.63 μg/g MMA was found in medium for P1, and less for sample P2. Cell viability: Both cell lines displayed a viability decrease, but remained above 75%, compared to controls, when exposed to undiluted samples. Inflammation: proinflammatory molecule TNF-α decreased when DOK cultures were exposed to G-AgNp samples. MDA levels indicated increased oxidative stress damage in cells treated with PMMA, confirmed by the antioxidant mechanism activation, while samples containing G-AgNp induced an antioxidant effect. All tested samples showed antibacterial properties against Gram-positive bacteria. Samples containing G-AgNp also exhibited bactericide action on E. coli. Mechanical properties: both samples containing G-AgNp improved flexural strength compared to the sample resin, measured through elastic strength parameters. PMMA resin loaded with G-AgNp presents promising antibacterial activity associated with minimal toxicity to human cells, in vitro, as well as improved flexural properties. These encouraging results obtained in vitro support further in vivo investigation, to thoroughly check whether the PMMA loaded with graphene-silver nanoparticles constitute an improvement over current denture materials.