Released (co)monomers from dental composite components can induce DNA damage of which DNA double-strand breaks (DSBs) threaten genome integrity. Here, we tested whether the administration of the antioxidant N-acetylcysteine (NAC) is able to reduce the dental composite-induced DSBs in primary human gingiva fibroblasts. The dental composites Bis-GMA (bisphenol-Aglycerolate dimethacrylate), GMA (glycidyl methacrylate), HEMA (2-hydroxyethyl methacrylate) and TEGDMA (triethyleneglycol dimethacrylate) were found to induce co-localizing microscopic nuclear foci numbers of the DSB markers γ-H2AX and 53BP1 per cell in the order: GMA>Bis-GMA>TEGDMA>HEMA. Supplementation of (co)monomer-containing culture medium with NAC led to a significant reduction of resin-induced DSBs as well as to an amelioration of dental monomer-induced nuclear chromatin condensation in gingival fibroblasts. Thus, antioxidant treatment can reduce radical-induced chromatin and DNA damage and open avenues to mitigate genotoxic effects of dental composite compounds.