Zearalenone (ZEN) and its derivatives are non-steroidal estrogenic mycotoxins mainly produced by Fusarium species. They are widely distributed in grain feeds originated from maize, barley, wheat and sorghum, causing serious harm to animal and human health. Currently, there is a pressing need of an efficient technology for ZEN degradation and detoxification. Because traditional physical and chemical methods could not effectively detoxify ZEN in grains, and might also affect the grain nutrients and food taste, and even result in secondary pollution, the biological technologies are developed to detoxify ZEN and its derivatives. In this paper, we reviewed the structure of ZEN and its derivatives, the fungi and bacteria species with ability of degradation of ZEN. In addition, the characterization, protein sequences and conformation of currently identified ZEN degrading enzymes, the only solved ZHD structure from Clonostachys rose were analyzed and compared, and the enzymes heterologous expression and application were also reviewed. This review will provide reference for reducing the cost of ZEN degrading enzymes by biological technologies such as enzyme engineering and fermentation engineering.