Objective: To explore the improvement effect of small molecule immunomodulator combined with budesonide, glycopyrronium bromide and formoterol fumarate on airway mucus hypersecretion, immune function and inflammatory response in the treatment of chronic obstructive pulmonary disease (COPD). Methods: A total of 120 patients with COPD who were treated in qingfeng county people"s hospital from January 2023 to December 2024 were selected as research subjects, and they were randomly divided into treatment group and control group by drawing lots, with 60 cases in each group. Both groups were treated with budesonide, glycopyrronium bromide and formoterol fumarate, and the treatment group was combined with thymosin α1 on this basis. After 3 months of treatment, the clinical efficacy in the two groups was recorded. The levels of airway mucus hypersecretion related indexes [mucin 5AC (MUC5ac), Toll-like receptor 4 (TLR4), sputum dry/wet specific gravity], immune function (T lymphocyte subsets CD4+, CD8+, CD3+) and serum inflammatory indexes [Hypersensitive C-reactive protein (hs-CRP), interleukin-8 (IL-8), procalcitonin (PCT)] were compared before treatment and after 3 months of treatment, and the adverse reactions during treatment were recorded. Results: After 3 months of treatment, the total effective rate in treatment group was higher than that in control group (P<0.05). The sputum dry/wet specific gravity, MUC5ac, CD8+, hs-CRP, IL-8 and PCT in the two groups were significantly decreased, and the indexes in treatment group were lower than those in control group (P<0.05). The levels of TLR4, CD4+ and CD3+ were significantly increased, and the levels were higher in treatment group than those in control group (P<0.05). There were no significant differences in the incidence rates of adverse reactions (P>0.05). Conclusion: Small molecule immunomodulator combined with budesonide, glycopyrronium bromide and formoterol fumarate in the treatment of COPD can effectively alleviate the airway mucus hypersecretion status, enhance the body’ s immune function, relieve the inflammatory response, and improve the clinical effect, with good safety.