Droughts not only reduce the biomass of sorghum (Sorghum bicolor (L.) Moench) but also increase the risk of hydrogen cyanide (HCN) toxicity to animals, mainly due to increased HCN content in drought-stressed plants. In the present study, the variations of HCN contents in 12 sorghum genotypes (10 sweet sorghum cultivars, one Sudangrass and one forage sorghum) were investigated at jointing, filling and ripening stages under rainfed conditions. Next, three genotypes – one sweet sorghum, one Sudangrass and one forage sorghum – were further selected to elucidate the physiological mechanisms of plant growth regulators (PGRs) (abscisic acid (ABA) and methyl jasmonate (MeJA)) in mitigating the concentrations of HCN in drought-stressed plants in a pot experiment. About 100 µg/L ABA and 100 µg/L MeJA were sprayed separately or together twice on drought-stressed (50 and 75% field water capacity) plant leaf. The drought lasted for 15 days. In the field experiment the HCN content in plants reduced from jointing to filling stages then increased from filling to ripening stages in several cultivars. In the pot experiment, drought increased the HCN accumulation and soluble protein content in leaves of all three genotypes. PGRs overall reduced the HCN contents in drought-stressed sweet sorghum and Sudangrass but not in forage sorghum (except in the ABA+MeJA treatment). However, the soluble protein contents were reduced by PGRs in drought-stressed forage sorghum but not in sweet sorghum (except in the ABA+MeJA treatment) and Sudangrass. Both ABA and MeJA increased the plant weights, whereas only MeJA enhanced net photosynthetic rate (P_N) in all three genotypes. PGRs reduced release rate of superoxide and hydrogen peroxide and malondialdehyde in all drought-stressed plants, and reduced the activities of peroxidase, superoxide dismutase, catalase, and ascorbate peroxidase in sweet sorghum but not in other two genotypes. These results suggest that exogenous ABA and MeJA could increase plant weight and reduce HCN content in drought-stressed sorghums, with varying physiological responsive mechanisms among sorghum genotypes.