Sorghum (Sorghum bicolor L. Moench) is a vital drought-tolerant crop cultivated in arid and semi-arid regions, serving as both food and fodder. However, under environmental stress, sorghum accumulates cyanogenic glucosides (primarily dhurrin), which hydrolyze into toxic hydrogen cyanide (HCN) upon ingestion, posing lethal risks to livestock. This review examines the biochemical pathways of dhurrin synthesis and HCN release, highlighting key risk factors including drought, frost, and improper grazing management. This study is structured to first elucidate the biochemical and risk factors behind sorghum poisoning, then to evaluate a suite of integrated mitigation strategies—from agroforestry to genetic solutions—and finally to discuss the implementation pathways through education and policy.We evaluate mitigation strategies such as agroforestry integration—using nitrogen-fixing trees (Leucaena leucocephala, Gliricidia sepium) to reduce plant stress and provide alternative fodder—alongside feed management techniques (ensiling, sulfur supplementation). Additionally, we explore genetic solutions (low-dhurrin cultivars developed via CRISPR-Cas9) and microbial/phytoremediation approaches (Pseudomonas fluorescens, Eucalyptus camaldulensis) for cyanide detoxification. Farmer education on risk recognition and safe practices emerges as a critical preventive measure. By synthesizing current research, this paper proposes integrated, sustainable strategies to minimize sorghum poisoning while maintaining agricultural productivity in vulnerable regions.