Drought as water deficit in the soil represents the most commonly occurring and the most variable environmental stress factor worldwide. Plants have evolved various strategies to cope with drought stress in relation to their other needs and processes such as the necessity to supply carbon for photosynthetic assimilation in plants with a C3 type of photosynthetic assimilation. In the present study, two wheat cultivars, Baletka and Tobak, representing two contrasting strategies, were studied at physiological, proteomic and metabolomics levels to provide a complex view on their phenotypic responses to drought treatment. Physiological characteristics clearly distinguished Baletka and Tobak and, moreover, in water-saving Baletka both proteomics and metabolomics analyses revealed significant remodelling of cell wall, changes in endocytosis and cell signalling, and especially, changes in synthesis of other defence proteins and LTI 65 kDa protein (also known as RD29B protein), which has been detected in wheat for the first time. An amazing finding was the enhanced accumulation level of oxalate oxidase implying enhanced oxaloxidase activity leading to faster degradation of oxalate with the simultaneous gain of two molecules of CO2, which may represent an alternative source of CO2 for plants with C3 type of photosynthesis suffering under drought stress.