Arsenic (As) toxicity is a problem that needs to be solved in terms of both human health and agricultural production in the vast majority of the world. The presence of As causes biomass loss by disrupting the balance of biochemical processes in plants and preventing growth/water absorption in the roots and accumulating in the edible parts of the plant and entering the food chain. A critical method of combating As toxicity is the use of biosafe, natural, bioactive compounds such as hesperidin (HP) or chlorogenic acid (CA). To this end, in this study, the physiological and biochemical effects of HP (100 μM) and CA (50 μM) were investigated in Zea mays under arsenate stress (100 μM). Relative water content, osmotic potential, photosynthesis-related parameters were suppressed under stress. It was determined that stress decreased the activities of the antioxidant system and increased the level of saturated fatty acids and, gene expression of PHT transporters involved in the uptake and translocation of arsenate. After being exposed to stress, HP and CA improved the capacity of superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and then ROS accumulation (H2O2) and lipid peroxidation (TBARS) were effectively removed. These phenolic compounds contributed to maintaining the cellular redox status by regulating enzyme/non-enzyme activity/contents involved in the AsA-GSH cycle. HP and CA reversed the adverse effects of excessive metal ion accumulation by re-regulated expression of the PHT1.1 and PHT1.3 genes in response to stress. Exogenously applied HP and CA effectively maintained membrane integrity by regulating saturated/unsaturated fatty acid content. However, the combined application of HP and CA did not show a synergistic protective activity against As stress and had a negative effect on the antioxidant capacity of maize leaves. As a result, HP and CA have great potentials to provide tolerance to maize under As stress by reducing oxidative injury and preserving the biochemical reactions of photosynthesis.