Deoxynivalenol (DON), a toxic secondary metabolite produced by Fusarium graminearum in infected cereal crops, has emerged as a major global contaminant in food and feed due to its stable physicochemical properties and resistance to degradation during conventional processing. This contamination poses a serious threat to livestock production and animal health. This review provides a comprehensive overview of the current status of DON contamination, its transmission through the food chain, metabolic pathways in animals, and the comparative toxicity of its metabolites. Furthermore, we analyze DON-induced toxic effects, including acute toxicity, cytotoxicity, immunotoxicity, neurotoxicity, gastrointestinal toxicity, and hepatotoxicity. By integrating domestic and international regulatory thresholds with current mitigation strategies, we highlight future research directions focusing on biodegradation technologies and genetic regulation approaches to alleviate DON contamination in livestock feeds. Advancing efficient DON-degradation strategies could open new avenues for sustainable feed management and mycotoxin detoxification technologies.