Drought stress is an inevitable challenges presents in various environments hindered plant biomass production and quality. Wheat crop productivity is hampered all over the world due to water stress. Therefore, exogenous treatments of plants with vitamins might be useful method to decrease drought growth and productivity losses. Thiamine and pyridoxine are organic nutritional agents needed for development of all living organisms. Cyanobacteria as biofertilizers are considered as environmentally friendly, cost-effective, and alternate to artificial and chemical fertilizers. Due to its physiological properties, cyanobacteria and vitamins are considered potential and environmentally friendly compound for agricultural plant protection and improvement productivity under diverse abiotic challenges such as drought. The aim of this investigation was to study the mechanism of thiamine (Th) or pyridoxine (Pyr) in the absence and presence of Cyanobacteria (Cya) in alleviating the reverse impacts of water deficit on wheat plant. A field experiment was conducted in the Farm of National Research Centre Nubaria region, Egypt. Plants were exposed to different leves of water irrigation requirements (100% or 75% WIR) and two concentrations of Th or Pyr (50, and 100 mg/l). Water stress decreased growth and grain yields and its components of wheat plant compared to 100% water irrigation requirement. Total solule sugars (TSS), proline (Pro) and total free amino acids (FAA) content increased under water-stressed and Th or Pyr treated plants, with and without of Cya. Meanwhile, foliar treatment of Th or Pyr in absence and presence of Cya increased markedly growth parameters, grain yield. Associating with an improvement of photosynthetic pigments, TSS, Pro and FAA. Furthermore, protein bands revealed in wheat treated with Th and Pyr without and with Cya at 100% and 75% WIR stimulates appearance of some polypeptides at 42 and 24 kDa. Also, one subunit at 18 kDa appeared in the presence of Cya at 75% and 100% WIR. Wheat plants treated with Th or Pyr increased density and intensity of protein bands at water deficit (75% WIR). Peroxidase and polyphenol oxidase isozymes were scored in wheat plant treated with Th and Pyr in without and with of Cya under water strees. In conclusion, exogenous treatment of thiamine and pyridoxine and cyanobacteria improved growth and productivity of wheat plants under normal water irrigation and could alleviate the reduced drought stress. The maximum growth and yield of wheat plant were gained at 100 mg-1 Pyr or Th in the presence of Cya.