Salt stress is one of the major constraints affecting plant growth and agricultural productivity worldwide. Sorghum is a valuable food source and a potential model for studying and better understanding the salt stress mechanics in the cereals and obtaining a more comprehensive knowledge of their cellular responses. Herein, we examined the effects of salinity on reserve mobilization, antioxidant potential, and expression analysis of starch synthesis genes. Our findings show that germination percentage is adversely affected by all salinity levels, more remarkably at 120 mM (36% reduction) and 140 mM NaCl (46% reduction) than in the control. Lipid peroxidation increased in salt-susceptible genotypes (PC-5: 2.88 and CSV 44F: 2.93 nmloe/g.FW), but not in tolerant genotypes. SSG 59-3 increased activities of α-amylase, and protease enzymes corroborated decreased starch and protein content, respectively. SSG 59-3 alleviated adverse effects of salinity by suppressing oxidative stress (H2O2) and stimulating enzymatic and non-enzymatic antioxidant activities (SOD, APX, CAT, POD, GR, and GPX), as well as protecting cell membrane integrity (MDA, electrolyte leakage). A significant increase (p ≤ 0.05) was also observed in SSG 59-3 with proline, ascorbic acid, and total carbohydrates. Among inorganic cations and anions, Na+, Cl-, and SO42- increased, whereas K+, Mg2+, and Ca2+ decreased significantly. SSG 59-3 had a less pronounced effect of excess Na+ ions on the gene expression of starch synthesis. Salinity also influenced Na+ ion efflux and maintained a lower cytosolic Na+/K+ ratio via concomitant upregulation of SbNHX-1 and SbVPPase-I ion transporter genes. Thus, we have highlighted that salinity physiologically and biochemically affect sorghum seedling growth. Based on these findings, we highlighted that SSG 59-3 performed better by retaining higher plant water status, antioxidant potential, and upregulation of ion transporter genes and starch synthesis, thereby alleviating stress, which may be augmented as genetic resources to establish sorghum cultivars with improved quality in saline soils.