The two direct dental restorative materials most commonly used today are silver-mercury amalgam and resin-based composites. The purpose of this study was to examine the effects of these two restorative materials and substances released by these into the oral environment on lipid peroxidation and DNA oxidation after entering the blood circulation.Blood samples from 41 patients were collected before and 24 hours after the application of these restorative materials. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in these samples was measured to determine oxidative DNA damage, and malondialdehyde levels were measured to define lipid peroxidation. The paired samples t test and Pearson correlation analysis were used for the analysis of variables (α = 0.05).While no statistically significant difference was observed after amalgam filling application in terms of DNA oxidation, a significant difference was observed after composite application (P < 0.05). Furthermore, a significant increase was determined in malondialdehyde levels of two materials (P < 0.05). In both amalgam and composite applications, a significant difference was observed before and after application in terms of released substances (mercury and unpolymerized monomer, respectively, P < 0.001).Mercury increased lipid peroxidation and Bis-GMA and TEGDMA dental resins increased both lipid peroxidation and DNA oxidation markers.