Mycotoxins are a class of important pollutants that seriously endanger food security, causing massive food waste and substantial economic losses. Zearalenone (ZEN) has become one of the representative type of mycotoxins owing to its wide range of contamination and high detection rate. With increasing ZEN contamination of food and increased biodegradation and targeting of ZEN, the food production industry has sought biodegradation techniques with enhanced safety and adaptability. We reviewed the identification of ZEN-degrading bacteria (Aspergillus niger, Myxoplasma rosea, etc.), the isolation and modification of ZEN-degrading enzymes (ZHD101, RmZHD, etc.), and the degradation of ZEN by cell factories combined with genetic engineering. The structure and toxicity of the degradation products produced therein, together with the degradation pathways and fate experienced, are analyzed. In future research, we intend to focus on screening and modifying ZEN-degrading enzymes with enhanced degradability and safety. Multi-selectivity and multi-targeting of biodegradation will also be developed for the degradation and removal of various ZEN derivatives. Notably, future biodegradation methods need to be closer to actual production, increase production adaptability, and be further studied with respect to stability and safety.