Purpose: Periodontitis generally initiates in the interdental area, where biofilm development is difficult to interrupt. Mechanical cleaning with interdental brushes (IDB) offers an effective method for plaque control and prevents gingivitis and periodontitis. This study aimed to determine whether mechanical cleaning with interdental brushes combined with the use of cetylpyridinium chloride (0.3% CPC) gel was more effective at plaque control compared with mechanical cleaning with interdental brushes alone. Materials and Methods: Forty individuals (30 - 70 years) with at least 20 teeth and moderate chronic periodontitis who had no experience with interdental cleaning aids were randomly assigned to a treatment group (brush + gel, n = 20) or a control group (brush, n = 20). Both groups were examined by a dentist at baseline and at 3 and 6 months for changes in interdental plaque [interproximal plaque index (API)] levels, gingival inflammation [sulcus bleeding index (SBI)], probing depth (PD), and bleeding on probing (BOP). Results: No baseline differences in age, gender, or number of teeth were observed between the two groups. During the study period, improvements in API and BOP were comparable between groups. However, improvements in SBI and PD were significantly greater in the test group than in the control group (P = 0.046 and P = 0.029, respectively). Conclusion: Mechanical interdental plaque control with interdental brushes combined with the use of CPC gel significantly improved 6-month gingival and periodontal outcomes (SBI and PD) compared with mechanical cleaning with interdental brushes alone.