Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium spp. that mainly contaminates wheat, corn, and other food crops, and has posed serious threats to food safety. Currently, enzymatic detoxification of DON shows promising application prospects. This paper provided an overview of the latest domestic and international research on the types of biotransformation enzymes, degradation mechanisms, structural features, detoxification enzyme mining strategies, and molecular modifications of DON. Additionally, the paper explored research trends in molecular design of mycotoxin detoxification enzymes assisted by artificial intelligence, which aimed to provide a reference for the development of bio-detoxification technology of DON in food and feed.