Drought stress (DS) is a considerable limiting factor that reduces growth and crop productivity. Melatonin (MT) is one of the emerging plant hormones involved in improving drought tolerance in plants. Therefore, the current study was comprised of various MT levels i.e., control, 100, 200, and 300 μM factorially combined with four sorghum genotypes: YSS-1, YSS-15, Johr, and PARC-S-4. The DS was imposed at the initiation of booting (Zadoks growth scale) by withholding irrigation for 1 week. Taller plants (74.7 cm), with more leaves per plant (LLP: 12), flag leaf area (FLA: 153.7 cm2), root and shoot ratio (0.16), biomass yield (89.1 g), Brix value (9.7%) and soluble solids (SS: 13.3) were recorded with the application of 300 μM MT. In the case of cultivars YSS-1 performed with maximum plant height (74.7 cm), LPP (11), FLA (143.9 cm2), root and shoot ratio (0.14), biomass yield (87.2 g), Brix value (10.3%) and SS (11.5). The activities of antioxidants (CAT, POD, and SOD) were also significantly increased after the imposition of DS, nonetheless, the application of MT further enhanced the activities of these antioxidants to confer drought tolerance. Therefore, these findings suggested that foliar spray of MT (300 μM) could alleviate the negative impacts of DS and improve the growth, biomass yield, and nutritional quality of sorghum. •Melatonin (Mel) could improve drought tolerance in plants.•Mel improved plant height, LLP, FLA, SS, root/shoot ratio, biomass yield, brix value.•Endogenous antioxidants activity was increased by drought stress, and further by Mel.•Foliar spray of Mel (300 μM) alleviates drought stress negative impacts.•Foliar spray of Mel improves sorghum growth, biomass yield and quality.