Abstarct: The presence of heavy mextals has harmful effects on the environment and agricultural production. Given the increasing spread of industrial pollutants and wastes and the ever-increasing pollution of the environment, it seems necessary to adopt solutions to deal with this major problem. This study aimed to evaluate the physiological and biochemical responses of Trigonella foenum-graecum (fenugreek) to dopamine application (0 and 200 µM) and non-thermal plasma treatment (two exposure durations: 2 and 4 minutes; two voltages: 4 and 6 kV, at 20 kHz frequency) under cadmium (300 µM/L) and chromium (300 µM/L) stress, with a focus on the changes in their accumulation in the aerial parts of the plant. According to the findings, dopamine and non-thermal plasma significantly modulated the physicochemical and biochemical responses of fenugreek under cadmium and chromium stress by stimulating the plant’s defense mechanisms, ultimately enhancing its stress tolerance. The application of these two treatments in mextal-exposed plants resulted in increased levels of photosynthetic pigments, relative water content, enzymatic and non-enzymatic antioxidant activities, as well as elevated concentrations of sugars, phenolics, and proline. Conversely, hydrogen peroxide content, malondialdehyde levels, and electrolyte leakage were significantly reduced. Furthermore, non-thermal plasma treatment at 6 kV for 2 minutes decreased cadmium and chromium accumulation in the plant by 18% and 30%, respectively. Similarly, dopamine application in plants exposed to cadmium and chromium resulted in reductions of 14% and 24% of these mextals in the aerial tissues.These results indicate that the combined application of non-thermal plasma and dopamine reinforces the plant’s defense mechanisms and modulates mextabolic activities in fenugreek, culminating in reduced cadmium and chromium uptake. The outcomes of this study may also provide insights for the remediation of soils contaminated with radioactive nuclear materials.