Cadmium is a toxic heavy metal that causes environmental pollution. High concentrations of cadmium in the soil have undesirable influences on plants' biochemical and physiological characteristics. Iron has potential to minimize the harmful effects of cadmium, improve growth characteristics and increase the antioxidant potential of plants. In the present study, lettuce plants were treated with the different concentrations of cadmium chloride (0, 200, 400, and 600 mu M), nano-chelated iron (0.5 and 1 g/L), and their combinations. Although growth indices have decreased in the presence of cadmium, the application of nano-chelated iron to cadmium-treated plants improved growth parameters. In the combined treatments of cadmium chloride and nano-chelate iron, the activity of some antioxidant enzymes such as catalase, peroxidase, ascorbate peroxidase, and superoxide dismutase have increased by amounts of 0.138, 0.249, 1.557, 9.943 U/mg protein, respectively compared to plants treated with cadmium chloride alone. Similarly, exposure of plants to cadmium chloride and nano-chelated iron increased proline content, relative water content, and 2,2-diphenyl-2-picrylhydrazyl radical scavenging activity in comparison to the control group. The application of nano-chelated iron in plants treated with cadmium chloride resulted in a decrease in hydrogen peroxide and malondialdehyde content. Altogether, the data revealed that simultaneous supply of nano-chelated iron may reduce the toxicity and destructive impacts of cadmium chloride in lettuce plants. Additionally, the application of nano-chelated iron on plants under cadmium chloride stress can introduce new strategies to manage/mitigate oxidative stress caused by heavy metal exposure.