Diosgenin is a botanical steroidal saponin with anti-inflammatory, antioxidant, anti-thrombotic, anti- apoptotic, anti-depressant, and anti-nociceptive properties. However, it's unknown how diosgenin affects anti-nociception. TRPV1, a transient receptor potential vanilloid, is crucial for nociception. Therefore, we investigated whether TRPV1 antagonism mediates the anti-nociceptive effects of diosgenin. In vivo mouse experiments were performed to examine nociception-related behavior, while in vitro experiments were per-formed to examine calcium currents in dorsal root ganglion (DRG) and Chinese hamster ovary (CHO) cells. The duration of capsaicin-induced licking (pain behavior) was significantly reduced following oral and intraplantar administration of diosgenin, approaching levels observed in mice treated with the TRPV1 antagonist BCTC. Additionally, oral administration of diosgenin reduced capsaicin-induced thermal hyperalgesia. Further, diosgenin reduced capsaicin- induced Ca2+ currents in a dose-dependent manner in both DRG and CHO cells. Oral administration of diosgenin also improved thermal and mechanical hyperalgesia in the sciatic nerve constriction injury- induced chronic pain model by reducing the expression of TRPV1 and inflammatory cytokines in DRG cells. Overall, our findings imply that diosgenin has analgesic benefits in a mouse model of neuropathic pain by inhibiting TRPV1 and reducing inflammation in the DRG.