Helminth infection or their derived molecules (mainly ESPs) can lead to a broad range of outcomes that ameliorate WD-induced obesity and metabolic disorders, including M2 polarization of macrophages (Figure 1), down-regulation of metabolic inflammation by triggering the release of type 2 cytokines (such as IL-4, IL-10, and IL-13), the increase of thermogenesis and energy consumption by promoting fat browning, modification of adipokines and lipid metabolism, improvement of insulin sensitivity and glucose tolerance, and modulation of gut microbiota (Figure 2). Here, IL10 is linked to obesity due to melanocortin 4 receptor deficiency.