Salt stress is one of the major abiotic stress which severely limits plant growth and reduces crop productivity across the world. In the present study, the effects of exogenous pyridoxal-5-phosphate (vitamin B6, VB6) on seedling growth and development of wheat under salt stress were investigated. The results showed that exogenous application of pyridoxal-5-phosphate (VB6) significantly increased the RWC, biomass, the concentration of photosynthetic pigments, proline, the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), together with decreasing the content of Malondiadehyde (MDA) and hydrogen peroxide (H2O2) in wheat leaves under salt stress. Meanwhile, the transcript level of P5CR, P5CS, SOD, TaSOS1 and TaSOS4 were also up-regulated after treatment with pyridoxal-5-phosphate. VB6 acts as a signal in regulating the activities of plant antioxidant enzymes and SOS pathway to improve resistance to salt stress. The current study results may give an insight into the regulatory roles of VB6 in improving salt stress and VB6 could be an easily and effective method to improve salt-stress tolerance to wheat in the field condition. It is urgency to understand the molecular mechanism of VB6 to enhance the salt tolerance of wheat in the next work.