Multiple myeloma (MM) patients are often accompanied by heightened levels of oxidative stress, even following bone marrow transplantation. Trace mineral supplements have been found to regulate and inhibit the activity of oxidative radicals and inflammatory factors, which are involved in the pathogenesis of MM. The study sought to evaluate the effectiveness of the supplementation by analyzing changes in oxidative, anti-oxidative, and inflammation markers. Patients were randomly assigned to a zinc or placebo group, with the former receiving 30mg of zinc or placebo tablets daily for 1month. Blood samples were collected from the patients on the day of transplantation, 15days, and 30days post-transplantation. Real-time PCR was employed to measure the expression of oxidative/antioxidative genes. Furthermore, the protein level of oxidative markers in serum samples was assessed. Finally, serum TNF-α concentrations were measured using the ELISA technique. The expression levels of SOD1, SOD2, and NRF2 genes were significantly higher on days 15 and 30 compared to the control group (P < 0.05), with a greater increase on day 30 (P < 0.05). Conversely, the expression levels of Keap1 and NOX2 genes were lower on day 30 than those of the control group (P < 0.05), with a further decrease from day 15 to day 30 (P < 0.05). The experimental group exhibited a notable reduction in TNF-α cytokine levels on day 30 compared to the control and placebo groups (P < 0.05). All findings were coordinated according to the nutritional questionnaire. Our findings suggest a potential benefit of zinc supplementation in managing the adverse effects of chemotherapy in MM patients, warranting further investigation.