Background: Hederacoside C from ivy leaf dry extracts (HH) and berberine from Coptidis rhizome dry extracts (CR) can be combined (HHCR) as a herbal product. Previous studies have demonstrated that HHCR has antitussive and expectorant effects in animal models of respiratory disease. However, the therapeutic effects of HHCR on respiratory diseases in humans have not been well-studied. Therefore, we aimed to clarify the effectiveness of HHCR in patients with chronic bronchitis and bronchiectasis. Methods: This was a multicenter (10 university teaching hospitals), open-label, prospective, single-arm, observational study. Consecutive patients with chronic bronchitis and bronchiectasis were included. Patients were orally treated with HHCR daily for 12 weeks. St. George’s Respiratory Questionnaire (SGRQ) scores and bronchitis severity scores (BSS) were measured at baseline and at the end of the 12-week study. Results: In total, 376 patients were enrolled, of which 304 were finally included in the study, including 236 males and 68 females with a median age of 69 years (range: 37–88 years). After 12 weeks of HHCR treatment, there was a significant improvement in SGRQ score (baseline, 32.52 ± 16.93 vs. end of study, 29.08 ± 15.16; p < 0.0001) and a significant reduction in BSS (baseline, 7.16 ± 2.63 vs. end of study, 4.72 ± 2.45; p < 0.0001). During the study, 14 patients concomitantly used an inhaled corticosteroid and 83 patients used an inhaled bronchodilator. HHCR also had significant positive effects on these patients in terms of SGRQ score and BSS. No serious adverse drug reactions occurred during HHCR treatment. Conclusions: treatment with HHCR improved the SGRQ score and BSS in patients with chronic bronchitis and bronchiectasis. HHCR may be a new therapeutic option for chronic bronchitis and bronchiectasis. Large-scale, randomized, double-blind, placebo-controlled clinical trials are warranted.