Plants are markedly affected by drought stress caused by fluctuations in global climate, reduction in rainfall and a decrease in soil fertility. Therefore, some mechanistic strategies to cope with adverse effects of drought stress are needed. Alpha lipoic acid (ALA), a potent antioxidant molecule, is known to function in abiotic stress tolerance. In the current study, we investigated the ALA-stimulated physiological role in tolerance to osmotic stress induced by polyethylene glycol in two maize (Zea mays L.) cultivars (cv. Helen and cv. Akpinar). Application of ALA increased the leaf water potential of maize cultivars under stressful and stress-free conditions but decreased lipid peroxidation and the hydrogen peroxide (H2O2) content. Additionally, enhanced activity of the antioxidant defense system was observed following ALA application. Exogenous ALA elevated the activities of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (GPX), glutathione reductase (GR) and monodehydroascorbate reductase (MDHAR) under osmotic stress as compared to seedlings not exposed to ALA. Conversely, ascorbate peroxidase (APX) activity was decreased by ALA application in both cultivars. Higher GR and MDHAR activities of both cultivars were simultaneously observed in ALA treatments under osmotic stress. Taken together, the data indicated that exogenous ALA may function in arranging resilience against osmotic stress by reducing oxidative damage through induction of the antioxidant machinery in maize cultivars.