Objectives. This study aims to evaluate the efficacy of hematoporphyrin monomethyl ether- (HMME-) mediated sonodynamic therapy (SDT) on experimental periodontal disease in rats. Methods. Periodontal disease was induced by submerging ligatures at the first maxillary molar subgingival region in forty-eight male SD rats. After 30 days, the ligatures were removed. The rats were randomly allocated into four groups; the experimental SDT group was treated through hypodermic injection of 40 μg/mL HMME and 3 W/cm2 low-intensity ultrasound irradiation (1 MHz, 600 s). Those in control groups received 40 μg/mL HMME alone (control 1 group) or 3 W/cm2 ultrasound irradiation alone (control 2 group) or were subjected to neither HMME nor ultrasound (control 3 group). After 10 days of treatment, all rats were euthanized, the maxilla was obtained for histological examination, and the alveolar bone level was evaluated by histometric analysis. Results. The control groups showed more bone loss (P < 0.05) after 10 days of treatment than the SDT group. There is no significant difference among the control groups (P > 0.05). Conclusions. HMME mediated SDT was an effective therapy of experimental periodontal tissue in rats.