Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan. However, the mechanisms underlying potential health benefits of this therapy are still unclear. Therefore, we investigated the effect of HELP exposure (9 kV/electrode+9 kV/ electrode, 30 min) on several cytokines and hormones using enzyme-linked immunosorbent assays in plasma samples obtained from healthy human subjects before and after a single treatment session. Immunoreactive interleukin (IL)-1β and IL-6 levels were significantly downregulated following HELP exposure. Under these treatment conditions, HELP exposure did not exert on immunoreactive IL-10, IL-18, transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) adrenaline, serotonin, histamine, neuropeptide Y, somatostatin, insulin, or dehydroepiandrosterone sulfate (DHEAS) levels. The activation of transient receptor potential melastatin 8 (TRPM8) induces the suppression of the levels of inflammatory markers. Therefore, we further examined the in silico docking