Introduction: Hyperglycemia in people with diabetes mellitus and its lack of control are associated with irreversible consequences. Glycation of proteins and enzymes, especially antioxidant enzymes in uncontrolled diabetes mellitus, affects these consequences. Consumption of bioactive compounds containing antioxidants and minerals as well as the use of adjunct therapies, such as cold atmospheric plasma therapy, can be effective in preventing and controlling the consequences of diabetes mellitus.Objective: In this research, we investigated whether cold plasma treatment of diabetic samples was effective in altering the activity of oxidative enzymes, some biochemical elements, and biochemical parameters.Methods: Thirty individuals with type 2 diabetes mellitus and 30 healthy individuals, as controls, participated in the study. The samples were exposed to cold argon plasma jet for 10 minutes (by a 10 kHz pulsed DC power supply with an amplitude up to 20.0 kV). The following contents of the serum samples of all participants were evaluated according to the instructions of the used kits before and after the cold argon plasma jet treatment: the activity of catalase, superoxide dismutase, and glutathione peroxidase enzymes; the concentration of glucose, hydrogen peroxide, and selenium binding protein 1 (as an indicator of blood selenium); and the concentration of copper, zinc, iron, and magnesium.Results: The activity of antioxidant enzymes and minerals significantly increased in diabetic samples treated with cold plasma (P value < 0.05). No significant changes were observed in the concentrations of glucose, hydrogen peroxide, or selenium binding protein 1 in diabetic samples treated with cold plasma.Conclusions: Using cold argon plasma jet as an adjunct method, which will reduce the glycation of enzymes and improve some minerals, can reduce the risk of diabetes complications in patients with diabetes mellitus.Keywords:Antioxidant enzymes, Cold plasma, Diabetes mellitus, Minerals.