There is great interest in developing strategies to reduce the detrimental effects of salinity on plant growth and crop yield. Plant-derived smoke containing many promotive and inhibitory compounds is known to influence seed germination and plant growth in a concentration-dependent manner. It has been suggested that smoke can also alleviate abiotic stress-induced growth inhibition in several plants. However, there is still a lack of comprehensive knowledge regarding smoke-mediated biochemical and molecular changes in plants grown under stress conditions. Here we show that smoke regulates the expression of some genes encoding transcription factors and antioxidant enzymes in wheat seedlings subjected to salt stress (150 mM NaCl). We found that smoke-water (0.1%) increased the expression levels of TaDREB1, TaWRKY2, TaWRKY19, CAT, and Cu/Zn-SOD in salt-treated seedlings. Smoke-water also enhanced the transcription of TaWRKY19 and Cu/Zn-SOD genes under normal growth conditions. In addition, smoke was found to modulate physiological responses of wheat seedlings to salinity. The results demonstrate that smoke-water increases total phenolic content and free radical scavenging activity under salt stress but it leads to a significant decrease in proline accumulation. In conclusion, the current study reveals that smoke, although not having a remarkable effect on growth at the concentration tested, can affect physiological, biochemical, and molecular processes in wheat seedlings exposed to short-term salt stress. Our data also indicate the need for long-term field experiments for a better understanding of the effect of smoke on plant growth in the presence of salinity.