Periodontitis is an inflammatory disorder of the periodontium, characterized by destruction of the tooth supporting tissues including alveolar bone and mediated by various pro-inflammatory mediators. Here, we demonstrated that HP08-0106, composed of four crude drugs-Gardenia jasminoides Grandiflora, Angelica gigas Nakai, Rehmannia glutinosa, and Schizonepeta tenuifolia in a weight ratio of 2:2:1:2, perturbs inflammatory responses, osteoclast formation in LPS-induced RAW 264.7 cells and alveolar bone resorption in ligature-induced periodontitis. HP08-0106 decreased the protein level of iNOS and COX2 as well as the secreted level of IL-1β, indicating that HP08-0106 has antiinflammatory effects. HP08-0106 also inhibited the expression of genes associated with osteoclastogenesis including c-Fos, MMP-9 and TRAP. Moreover, HP08-0106 exhibited a protective effect from alveolar bone loss in ligature-induced periodontitis animal models. Our results strongly suggest that HP08-0106 represent an important therapeutic tool to treat inflammatory disorders associated with bone loss such as periodontitis.