Mycotoxins are secondary metabolites produced by fungi in food and feed, which can cause serious health problems. Bioenzymatic degradation is gaining increasing popularity due to its high specificity, gentle degradation conditions, and environmental friendliness. We reviewed recently reported biosynthetic mycotoxin-degrading enzymes, traditional and novel expression systems, enzyme optimization strategies, food and feed applications, safety evaluation of both degrading enzymes and degradation products, and commercialization potentials. Special emphasis is given to the novel expression systems, advanced optimization strategies, and safety considerations for industrial use. Over ten types of recombinases such as oxidoreductase and hydrolase have been studied in the enzymatic hydrolysis of mycotoxins. Besides traditional expression system of