Trehalose regulates key physio-biochemical parameters, antioxidants, and the yield of plants exposed to a dry environment. A study was conducted to assess the regulatory roles of exogenously applied trehalose in drought-stressed sunflower plants. Two cultivars of sunflowers (Hysun 33 and FH 598) were subjected to drought stress (60% field capacity) and varying (0, 10, 20, and 30 mM) concentrations of trehalose. The data indicated that water stress significantly reduced the shoot length, root length, total soluble proteins, shoot Ca2+, root P, relative water content (RWC), and achene yield per plant. The foliar spray of trehalose was effective at improving plant growth, RWC, total soluble proteins, total soluble sugars, the activities of enzymatic antioxidants, Ca2+ (shoot and root), root K+, and the yield attributes. Exogenously supplemented trehalose considerably suppressed relative membrane permeability (RMP), but did not alter ascorbic acid, malondialdehyde, the total phenolics, shoot K+, or P (shoot and root) in both sunflower cultivars. The cv. Hysun 33 had better ascorbic acid, total soluble sugars, non-reducing sugars, shoot P, and root P than the other cultivar, whereas cv. FH 598 was relatively better at regulating RMP, malondialdehyde, peroxidase, and root Ca2+ concentration. Overall, exogenously supplemented trehalose, particularly at 10 mM, was effective at improving the physiochemical parameters and yield of sunflower plants under stress conditions. Therefore, a better performance of sunflower cv. Hysun 33 under drought stress can be suggested as a trehalose-induced enhancement of yield and oxidative defense potential.