Heavy metal pollution in agricultural soils, particularly in industrial areas, is a growing concern that can negatively affect plant growth, performance, and the health of herbal products. This two-year study evaluated the enzymatic and metabolic responses of five medicinal plant genotypes—Peppermint (Mentha piperita), Chamomile (Matricaria chamomilla), Thyme (Thymus vulgaris), Basil (Ocimum basilicum), and Rosemary (Rosmarinus officinalis)—exposed to various levels of Lead (Pb) and Cadmium (Cd) in heavy metal-contaminated soils of the Arak region.The split-plot factorial experiment was conducted in a completely randomized design with three replications over two consecutive years. Three levels of Lead (0, 200, 400 mg/kg soil) and three levels of Cadmium (0, 5, 10 mg/kg) were tested. At the end of each growing season, the activity of antioxidant enzymes, including Superoxide Dismutase (SOD), Catalase (CAT), Peroxidase (POD), the content of Malondialdehyde (MDA), and the total concentration of alkaloids, were measured. The results showed that exposure to Lead and Cadmium significantly (at the 1% level) affected all measured parameters in both years. Cadmium at a concentration of 10 mg/kg soil led to a significant increase in the activity of antioxidant enzymes, particularly SOD and CAT, by 42% and 37% in the first year, and 45% and 40% in the second year, respectively. Concurrently, MDA content increased by 55% and 58%, respectively. The combination of Pb400+Cd10 showed the highest level of lipid peroxidation at 68% in the first year and 71% in the second year. Under moderate stress, alkaloid levels increased by 18-20%, while severe stress significantly reduced alkaloid levels by 23-25%. In species-dependent responses, Rosemary (Rosmarinus officinalis) exhibited the strongest antioxidant defense system, while Basil (Ocimum basilicum) showed the highest level of lipid peroxidation. These findings emphasize the necessity of long-term monitoring of heavy metal contamination in agricultural soils and its impact on the quality and safety of medicinal plants, providing a reference for selecting heavy metal-tolerant genotypes in medicinal plant breeding programs.