Heavy metal (HM) pollution is a major threat to terrestrial ecosystems. Addressing it requires identifying native plant species that tolerate HMs while maintaining physiological function. This study evaluated the physiological responses, antioxidant defense mechanisms, and phytoremediation potential of the high-Andean species Adesmia subterranea Clos under cadmium (Cd 3, 4.5, and 6 mg L⁻¹) and mercury (Hg 0.8, 1.2, and 1.6 mg L⁻¹) in a semi-hydroponic system. Survival, growth performance, metal accumulation, bioconcentration factor (BCF), translocation factor (TF), oxidative stress biomarkers such as hydrogen peroxide (H₂O₂), and antioxidant responses including catalase (CAT), ascorbate peroxidase (APX), and glutathione (GSH) were assessed. Exposure to Cd reduced survival and decreased biomass in a concentration-dependent manner, whereas Hg did not affect survival and reduced biomass only at 0.8 mg L⁻¹. Both metals were efficiently taken up (BCF > 1); Cd was consistently retained in roots (TF < 1), while Hg translocation increased with dose (TF up to 0.79 at 1.6 mg L⁻¹). Cd and Hg exposure induced oxidative stress, evidenced by increased H₂O₂ accumulation and lipid peroxidation, which was accompanied by activation of antioxidant defenses. The APX activity and GSH levels increased significantly, while CAT showed a metal-specific response. These results indicate coordinated regulation of enzymatic and non-enzymatic antioxidant pathways to maintain redox homeostasis under HM stress. Overall, these results provide a preliminary indication of the potential of A. subterranea for phytostabilization in metal-contaminated Andean ecosystems.