Sorghum bicolor (L.) Moench, as the fifth most important cereal crop globally, plays an irreplaceable strategic role in ensuring food security, supporting feed production, and promoting the development of the brewing industry. Dhurrin, as cyanogenic glycoside unique to sorghum, exhibits a dual role in plant defense and industrial applications. On one hand, as a key stress-responsive metabolite, dhurrin enhances plant resilience against adverse stresses such as drought, salinity, and pests and diseases. On the other hand, upon tissue damage or during processing, dhurrin can be hydrolyzed by β-glucosidase to release toxic hydrogen cyanide (HCN), posing potential risks of livestock health and brewing quality. This paper systematically reviews the spatiotemporal distribution characteristics of dhurrin, elucidates its metabolic network (encompassing biosynthesis, activation, detoxification, and recycling) and regulatory mechanisms. Research indicates that the biosynthesis of dhurrin mainly relies on the sequential catalysis of cytochrome P450 enzyme family (CYP79A1 and CYP71E1), with the glycosylation reaction catalyzed by glycosyltransferases such as UGT85B1, and is completed through the cooperative reaction of multi-enzyme complexes; its activation process is closely related to the degree of plant tissue damage, and the hydrolysis action of β-glucosidase is a key step. In the field of animal feed utilization, residual dhurrin in insufficiently processed sorghum stalks or silage may induce HCN poisoning in animals, limiting its safety as feedstock. During the brewing process, cyanide released from dhurrin degradation can further react to form the carcinogen ethyl carbamate (EC), which poses a potential threat to the food safety of Baijiu (Chinese liquor). In response to the aforementioned risks, this paper summarizes multiple detoxification strategies, including physical pretreatment, enzyme inhibitors, and microbial degradation. More importantly, based on a deep understanding of the dhurrin metabolic pathway, this paper further proposes a feasible approach for developing non- or low-dhurrin sorghum germplasm through molecular breeding. By utilizing gene-editing technologies such as CRISPR/Cas9 to precisely knock out key biosynthetic genes, thereby reducing risks at the source. This research provides comprehensive theoretical support and practical guidance for the targeted regulation of metabolism, safe processing, and efficient utilization of dhurrin in sorghum, which is of great significance for promoting the green and sustainable development of the entire sorghum industry chain.