Purpose: Triphala is a combination of three medicinal plants, extensively used in Ayurveda since ancient times. Triphala mouthwash is used in the treatment of periodontal diseases because of its antimicrobial and antioxidant properties. The aim of this study is to compare the efficacy of triphala mouthwash with 0.2% chlorhexidine in hospitalized periodontal disease patients. Methods: In this double-blind, randomized, multicenter clinical trial, 120 patients were equally divided into three groups. Patients in group A were advised to rinse their mouths with 10 mL of distilled water, group B with 0.2% chlorhexidine, and group C with triphala mouthwash for 1 minute twice daily for two weeks. The plaque index (PI) and the gingival index (GI) were recorded on the first and the fifteenth day. Results: There was no significant difference when the efficacy of triphala was compared with 0.2% chlorhexidine in hospitalized patients with periodontal disease. However, a statistically significant difference was observed in PI and GI when both group B and group C were compared with group A and also within groups B and C, after 15 days (P<0.05). Conclusions: The triphala mouthwash (herbal) is an effective antiplaque agent like 0.2% chlorhexidine. It is significantly useful in reducing plaque accumulation and gingival inflammation, thereby controlling periodontal diseases in every patient. It is also cost effective, easily available, and well tolerable with no reported side effects.