Deoxynivalenol (DON), one of the most common mycotoxins threatening food production and safety, is contaminating wheat and other cereals worldwide. Developing an effective method to degrade DON in cereals is favorable to protect human health and reduce economic losses. This work aimed to study electrochemical degradation of DON at different conditions in aqueous solution and wheat grains for guiding practical application. In aqueous solution, electrochemical reduction degraded 49.36 ± 0.81% of DON at −9.0 V after 60 min; electrochemical oxidation readily degraded 100% of DON within 20 min at 1.5 V and was applied in wheat grains, degrading 91.07 ± 1.83%. The structure of degradation products was identified through mass spectrometry. Furthermore, toxicity of the products was evaluated by ECOSAR software. LC 50 and EC 50 of all products were higher than 598 mg/ L, and ChVs were higher than 111 mg/L, suggesting that all products are not harmful. Our developed electrochemical degradation method of DON in wheat grains does not add harmful chemicals and is environmentally friendly, which is potential to degrade DON in cereals.