The inflammatory response plays important roles in acne vulgaris and pain pathogenesis. In previous study, Esc-1GN with anti-inflammatory, antimicrobial, and lipopolysacchride (LPS) binding activity was identified from the skin of the frog Hylarana guentheri. Here, we report its therapeutic potentials for acne vulgaris and inflammatory pain. Esc-1GN destroyed the cell membrane of Propionibacteria acnes in the membrane permeability assays. In addition, bacterial agglutination test suggested that Esc-1GN triggered the agglutination of P. acnes, which was affected by LPS and Ca . Meanwhile, in vivo anti-P. acnes and anti-inflammatory effects of Esc-1GN were confirmed by reducing the counts of P. acnes in mice ear, relieving P. acnes-induced mice ear swelling, decreasing mRNA expression and the production of pro-inflammatory cytokines, and attenuating the infiltration of inflammatory cells. Moreover, Esc-1GN also displayed antinociceptive effect in mice induced by acetic acid and formalin. Therefore, Esc-1GN is a promising candidate drug for treatment of acne vulgaris and inflammatory pain.