The study firstly established oxidative stress injury model of human embryonic kidney cells (HEK293) by the induction of 2, 2-azobis (2-methylpropionamidine) dihydrochloride (AAPH) to evaluate the antioxidant activity of five wheat protein-derived peptides Leu-Tyr (LY), Pro-Tyr (PY), Tyr-Gln (YQ), Ala-Pro-Ser-Tyr (APSY) and Arg-Gly-Gly-Tyr (RGGY). Then, it used quantum chemistry and molecular docking techniques to predict the optimal configuration and binding effect of five wheat protein-derived peptides combined with 2, 2-azinobis- (3-ethylbenzthiazoline-6-sulphonate) (ABTS), and to explore the molecular mechanism of wheat protein-derived peptides. The results of cell test show that after the action of five wheat protein-derived peptides, the cell death rate significantly decreases to below 3.68% (P ＜ 0.05), and the generation of reactive oxygen species (ROS) induced by AAPH was significantly reduced (P ＜ 0.05), making the ROS content tend to normal levels. All five wheat proteinderived peptides show good total antioxidant capacity and free radical scavenging capacity of 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) (P ＜ 0.05). RGGY shows the strongest total antioxidant capacity, with an activity value of (1.46 ± 0.08) mmol/L Trolox, followed by APSY, YQ, PY and LY. The DPPH free radical scavenging ability of YQ is the strongest, with a scavenging rate of 61.34% ± 2.24%, followed by APSY, RGGY, PY and LY. The results of molecular docking show that the CDOCKER interaction energy (-CIE) scores of the five wheat protein-derived peptides are 13.3049, 13.3973, 13.4121, 16.7685 and 16.2683, respectively, which can effectively interact with ABTS, mainly through the formation of strong hydrogen bonds and hydrophobic forces between ABTS molecules to exert antioxidant activity.