Antimicrobial peptides play important roles in the innate immune system of various organisms, and they may also be considered to prevent the organisms from infections. In particular, β‐defensins, mainly produced in epithelial cells, are recognized as one of the major antimicrobial peptides in mammals, including humans. In this study, we showed that Lactobacillus helveticus SBT2171 (LH2171), one of the several species of lactic acid bacteria, upregulates the production of β‐defensins in oral epithelial cells in vitro. Moreover, LH2171 reduced the increase of proinflammatory cytokine expression, induced by Porphyromonas gingivalis stimulation, in gingival epithelial cells. These data suggested that LH2171 suppresses P. gingivalis‐induced inflammation by upregulating the expression of β‐defensins in gingival epithelial cells. We subsequently investigated the effects of LH2171 in vivo and revealed that β‐defensin expression was increased in the oral cavities of LH2171‐fed mice. Furthermore, LH2171 decreased alveolar bone loss, gingival inflammation, and amounts of P. gingivalis‐specific 16S ribosomal RNA in the gingiva of P. gingivalis‐inoculated mice. Taken together, our results showed that LH2171 upregulates the expression of β‐defensins in oral cavity, thereby decreasing the number of P. gingivalis consequently ameliorating the experimental periodontal disease.