Drought is one of the lethal environmental stress factors that diminish the crop production worldwide. In this study, we assessed the damaging effects of drought stress; imposed by 20% polyethylene glycol (6000) treatments on wheat seedlings, and investigated the possible roles of calcium and abscisic acid (ABA) in alleviating drought stress. The pretreatment of wheat seedlings with calcium and ABA has led to improvements in growth criteria, content of photosynthetic pigments and membrane integrity under drought stress treatment. As a defense mechanism, the activity of peroxidase, and content of proline have increased under drought stress, but deceased when the wheat seedlings have been pretreated with calcium. The application of the calcium channel blocker; lanthanum chloride (LaCl3) has confirmed the alleviating role of calcium to the drought stress damaging effects. In this study, amino acids content, total soluble proteins and carbohydrates have been analyzed to further assess the physiological effects of drought and the alleviating roles of calcium and ABA. The improvements in yield criteria including % of mature grains per spike and weight of grains per spike with calcium pretreatment have confirmed the prolonged effect of calcium in alleviating the damaging effects of drought stress on wheat plants. Taken together, data presented in this study showed that calcium treatment may represent a powerful agent to counterattack the lethal effects of drought stress on plants.