The present study was planned to investigate the effects of thymoquinone (TQ) and lycopene (LYC), known to possess pro-inflammatory and antioxidant properties, on oxidative DNA damage (8-hydroxy-2-cleoxyguanosine) in BHK-21 cell line treated with high glucose (FIG) and the antioxidant system. BHK-21 cell line was cultured with regular passages (5% FBS, 10% host serum, 1% L-glutamine, 1% penicillin/streptomycin - RPMI 1640, 5% CO2 and 95%, 37 degrees C incubation). MTT cell viability tests were conducted. Proliferative TQ and LYC and glucose IC50 values were determined. Control, study groups; glucose (285 mM), TQ (10 mu M), and LYC (50 mu M)) and cross groups were designed. After incubation, trypsinized cells were broken by the freeze/thaw method and analyzed. Oxidative DNA damage, TAS, TOS and OSI values were determined for the obtained samples. It was determined that 8-OHdG levels were affected by high glucose (p <= 0.05), they increased further with the administration of TQ and LYC in addition to HG. TOS and OSI values increased in all study groups when compared to the control (p <= 0.05), and TAS levels significantly decreased (p <= 0.05) with the administration of HG when compared to TQ and LYC groups. In conclusion, TQ and LYC administration in addition to high glucose exacerbated oxidative DNA damage and OSI, and decreased TAS when compared to TQ and LYC groups. The TQ and LYC dose and administration duration in addition to high glucose in the present study led to an improvement in oxidative balance in the BHK cell line.