Mycotoxin contamination of food and feed is posing a serious threat to the global food safety and public health. Biological detoxification mediated by enzymes has emerged as a promising approach, as they can specifically degrade mycotoxins into non-toxic ones. However, the low degradation efficiency and stability limit their further application. To optimize the enzymes for mycotoxin removal, modification strategies that combine computational design with their structural data have been developed. Accordingly, this review will comprehensively summarize the recent trends in structure-based engineering to improve the enzyme catalytic efficiency, selectivity and stability in mycotoxins detoxification, which also provides perspectives in obtaining innovative and effective biocatalysts for mycotoxins degradation.