The role of selenium nanoparticles (Se-NPs) in the mitigation of high-temperature (HT) stress in crops is not known. The uptake, toxicity and physiological and biological effects of Se-NPs under HT were investigated in grain sorghum [ Sorghum bicolor (L.) Moench]. Se-NPs of size 10–40 nm were synthesized and characterized to indicate nanocrystalline structure. A toxicity assay showed that Se-NPs concentration inducing 50% cell mortality (TC50) was 275 mg L –1 . Translocation study indicated that Se-NPs can move from root to shoot of sorghum plants. Foliar spray of 10 mg L –1 Se-NPs during the booting stage of sorghum grown under HT stress stimulated the antioxidant defense system by enhancing antioxidant enzymes activity. Furthermore, it decreased the concentration of signature oxidants. Se-NPs facilitated higher levels of unsaturated phospholipids. Se-NPs under HT stress improved the pollen germination percentage, leading to a significantly increased seed yield. The increased antioxidant enzyme activity and decreased content of oxidants in the presence of Se-NPs were greater under HT (38/28 °C) than under optimum temperature conditions (32/22 °C). In conclusion, Se-NPs can protect sorghum plants by enhanced antioxidative defense system under HT stress.