The melatonin effects on Chagas disease are most likely due to the immunomodulator capacity, antioxidant role through the activation of NRF2, which can increase the gene expression of superoxide dismutase (SOD) and GSH, an anti-inflammatory action through the decreasing of the NF-κB pathway, which leads to the decrease of the gene expression of inflammatory cytokines. The gene discussed is SOD1; the disease is Chagas disease.