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Abstract Background This study aimed to evaluate the antiplaque and antibacterial effects of a mouthwash containing Lespedeza cuneata (LC) extract through clinical periodontal disease (PD) indicators and changes in PD-causing bacteria. Methods A total of 63 subjects participated in this double-blind clinical trial. Subjects were divided into two groups: 32 participants gargled with LC extract, and 31 used saline. Scaling was performed 1 week before the experiment to secure the homogeneity of the subjects’ oral conditions. After gargling with 15 ml of each solution for 1 min, participants spit out the solution to remove any residual mouthwash solution. Then, PD-related bacteria were measured via the O’Leary index, plaque index (PI), and gingival index (GI). The clinical data were collected three times: before gargling, immediately after gargling, and 5 d after gargling. Results After 5 d, the O’Leary index, PI, and GI scores were significantly reduced in the LC extract gargle group (p |