In plants, α-Lipoic acid (ALA) is considered a dithiol short-chain fatty acid with several strong antioxidative properties. To date, no data are conclusive regarding its effects as an exogenous application on salt stressed sorghum plants. In this study, we investigated the effect of 20 µM ALA as a foliar application on salt-stressed sorghum plants (0, 75 and 150 mM as NaCl). Under saline conditions, the applied-ALA significantly (p ≤ 0.05) stimulated plant growth, indicated by improving both fresh and dry shoot weights. A similar trend was observed in the photosynthetic pigments, including Chl a, Chl b and carotenoids. This improvement was associated with an obvious increase in the membrane stability index (MSI). At the same time, an obvious decrease in the salt induced oxidative damages was seen when the concentration of H₂O₂ and malondialdehyde (MDA) was reduced in the salt stressed leaf tissues. Generally, ALA-treated plants demonstrated higher antioxidant enzyme activity than in the ALA-untreated plants. A moderate level of salinity (75 mM) induced the highest activities of superoxide dismutase (SOD), guaiacol peroxidase (G-POX), and ascorbate peroxidase (APX). Meanwhile, the highest activity of catalase (CAT) was seen with 150 mM NaCl. Interestingly, applied-ALA led to a substantial decrease in the concentration of both Na and the Na/K ratio. In contrast, K and Ca exhibited a considerable increase in this respect. The role of ALA in the regulation of K⁺/Na⁺ selectivity under saline condition was confirmed through a molecular study (RT-PCR). It was found that ALA treatment downregulated the relative gene expression of plasma membrane (SOS1) and vacuolar (NHX1) Na⁺/H⁺ antiporters. In contrast, the high-affinity potassium transporter protein (HKT1) was upregulated.