Solar ultraviolet B (UVB) radiation is known to incite excessive inflammatory reactions that compromise the integrity of the skin's epidermal barrier and may ultimately contribute to the onset of skin carcinoma. Prior investigations have determined that following exposure to UVB, epidermal keratinocytes commence the synthesis of β-endorphin, a peptide derived from proopiomelanocortin, which possesses an analgesic property. Nonetheless, the specific functionality of β-endorphin within the context of skin subjected to UVB exposure remains inadequately elucidated. The current study thus pursued an investigation of the role that β-endorphin assumes in mediating protection against the deleterious impact induced by UVB irradiation on skin barrier mechanisms within normal human keratinocytes (NHKs) and a human skin equivalent model. Upon administering β-endorphin to NHKs subjected to UVB radiation, a downregulation of inflammatory response was observed, which was attributed to the suppression of the NF-κB signaling cascade. Evidence was also procured indicating that β-endorphin application mitigated the UVB-evoked aberrations in epidermal proliferation and differentiation within NHKs, subsequently leading to the restoration of barrier functions in skin equivalents subjected to UVB treatment. The mitigative properties of β-endorphin on NHKs affected by UVB radiation were found to be mediated through the inhibition of the Akt/mTOR signaling pathway. These findings suggest that β-endorphin possesses therapeutic potential for the amelioration of skin injuries resulting from UVB exposure, including the disruption of barrier functions of the skin.