Aim and Background: The present study was planned to investigate the effects of lycopene, on the caspase-dependent apoptosis in high-dose glucose (HG)-treated PC12 cell line. PC12 cells were cultured in vitro. Materials and Methods: HG was prepared as G (250 mM), and lycopene was prepared as L1 (10 μM), L2 (20 μM), and L3 (40 μM). After 6 h of incubation, the cells were exposed to trypsin, and the samples were obtained with freeze/thaw method. Caspase 3, 8, 9; 8-hydroxy-2-deoxyguanosine (8-OHdG); and M30 were determined (enzyme-linked immunosorbent assay). Results: 8-OHdG increased in L3 (P ≤ 0.001), whereas L1 caused a decrease in HG group (P ≤ 0.001). Caspase-3 decreased significantly in L1, L2, and L3G compared to control (P ≤ 0.001) group. Caspase-8 increased significantly in L1, L1G, L2G, and all L3 glucose groups (P ≤ 0.001). There was no difference for Caspase-9. M30 was not affected by L and HG, which decreased significantly (P ≤ 0.001). Conclusion: As a result, it was determined that, when PC12 cell line was treated with HG, lycopene application had effects on caspase enzymes and DNA damage.