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Background: Chronic obstructive pulmonary disease (COPD) as one of the health-threatening problems imposes many economic costs on health systems. Today, there is a greater tendency to use complementary and alternative therapies in the treatment of diseases. This study aimed to evaluate the efficacy of a Persian herbal formulation in patients with COPD. Materials and Methods: This randomized clinical trial was conducted on 76 patients with mild-severe COPD assigned to 2 groups (in each group n=38) for 8 weeks. The interventional group received Compound Honey Syrup (CHS), consisting of combination of honey and extracts of five medicinal plants (i.e., ginger, cinnamon, saffron, cardamom, and galangal) and the control group received a placebo. The COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ), and lung function test were used before and after. Results: Seventy-six patients, 88.6% male and 55.7% under 60 years of age, completed the course of treatment. At the end of the study, the overall score of the CAT questionnaire was significantly different between the first and fourth week (P=0.029). Meanwhile the findings of SGRQ questionnaire were significantly different between the interventional and control groups at other times (P=0.001). FEV1 and FEV1/FVC were found to be significantly different between two groups in weeks 4 and 8 (P <0.05). At the end of the study, no side effects of CHS were reported. Conclusion: Based on the data presented herein, CHS could be effective as a complementary and safe drug in increasing the quality of life of with COPD. [ABSTRACT FROM AUTHOR]