Objective(s): Chronic obstructive pulmonary disease (COPD) is a progressive airway condition characterized by chronic inflammation, oxidative stress, and tissue remodeling. Conventional treatments offer limited benefits in halting disease progression, prompting increased interest in natural agents with antioxidant and anti-inflammatory properties. This study aimed to evaluate the therapeutic effects of Origanum onites L., Origanum minutiflorum, and honey in a rat model of elastase-induced COPD. Materials and Methods: Thirty-eight female Wistar albino rats were divided into five groups: Control, COPD, O. onites L. treatment, O. minutiflorum treatment, and honey treatment. COPD was induced via intratracheal porcine pancreatic elastase. Treatments were administered orally for 15 days. Serum levels of IL-1 a, IL-33, and HMGB1, and lung homogenate levels of MMP-9 and TIMP-1 were measured by ELISA. T cell subtypes (CD3+, CD4+, CD8+) were analyzed by flow cytometry. Blood gas parameters were evaluated, and histopathological scoring was performed. Results: Origanum onites L., O. minutiflorum, and honey exhibited modulatory effects on inflammatory and oxidative markers. O. minutiflorum significantly reduced IL-1 a and IL-33 levels (P<0.05) and decreased MMP-9 expression. The honey group showed increased TIMP-1 levels and significantly improved blood oxygenation (pO2 and sO2). CD3+ and CD8+ T cell percentages were significantly higher in the treatment groups compared to the COPD group. Emphysema scores were significantly lower in the honey group (P<0.05), and lymphoid aggregates were observed only in the COPD group. Conclusion: The findings indicate that Origanum species and honey may have therapeutic potential for COPD by modulating inflammation, the immune response, and the protease-antiprotease balance. Further molecular and clinical studies are warranted.