The rising concentration of cadmium (Cd) builds a harmful effect on human and plant health associated with food chain contagion. Melatonin (MT) is an indole compound. Hence, the experiment was conducted to understand the physiological and biochemical mechanism of Cd detoxification by exogenous MT in tomato. Pots were filled with 30 ppm of Cd spiked soil and different concentration of exogenous MT was given to the plants through seed treatment (250 ppm), foliar spray viz., 25, 50, and 100 ppm, and both, whereas the foliar spray was given at 30 days after transplanting (DAT) and 46 DAT. When the plants are exposed to Cd stress, it reduces the gas exchange characters. The results revealed that foliar spray of 25 ppm of exogenous MT recorded the highest photosynthetic rate, stomatal conductance, and osmotic potential. MT had a direct interaction with reactive oxygen species scavenging by elevating endogenous antioxidant enzymes as well as the metabolites in plants. The contribution of MT foliar spray of 25 ppm at 30 and 46 DAT can mitigate Cd stress and it has potential implications for ensuring food safety and food security in marginal agriculture.