Heavy metal stress is a significant factor in diminishing crop yield. Plant-derived smoke (PDS) has been used as a growth promoter and abiotic stress alleviator for the last two decades. Although the roles of PDS have been determined in various plants, its role in ameliorating heavy metal stress in wheat has not been reported so far. Therefore, the present work was conducted to investigate the effect of smoke solution extracted from a wild lemongrass Cymbopogon jwarancusa (C. jwarncusa) on physiological and biochemical features of wheat under arsenic (As) and mercury (Hg) stress. The results showed that higher concentrations of As and Hg pose inhibitory effects on wheat seed germination and seedling growth, including shoot/root length and shoot/root fresh weight. Photosynthetic pigments, such as chlorophyll a and b and carotenoids, were significantly decreased under As and Hg stress. Importantly, the levels of H2O2, lipid peroxidation, and TBARS were increased in wheat seedlings. The activity of antioxidant enzymes, such as CAT, was decreased by As and Hg stress, while the levels of SOD, POD, and APX antioxidant enzymes were increased in root and shoot. Interestingly, the application of PDS (2000 ppm), individually or in combination with either As or Hg stress, enhanced wheat seed germination rate, shoot/root length, and shoot/root fresh weight. However, the levels of H2O2, lipid peroxidation, and TBARS were decreased. Similarly, the levels of SOD, POD, and APX were decreased by PDS under As and Hg stress, while the level of CAT was enhanced by PDS under As and Hg stress. Interestingly, the levels of chlorophyll a and b, and total carotenoids were increased with the application of PDS under As and Hg stress. It is concluded that PDS has the capability to alleviate the phytotoxic effects of As and Hg stress in wheat by modulating the antioxidative defense system and could be an economical solution to reduce the heavy metal stress in crops.