Abstract: Objective To investigate the clinical efficacy of microecological agents combined with dietary fiber in the treatment of chronic obstructive pulmonary disease (COPD) and its impacts on intestinal flora and inflammatory factors in patients. Methods A total of 80 patients with acute exacerbation of COPD were enrolled and randomly divided into dietary fiber group and combination group, with 40 patients in each group. The dietary fiber group received dietary fiber intervention, while the combination group received microecological agents combined with dietary fiber intervention. Nutrient intake, body mass index (BMI), nutritional indicators albumin (ALB), hemoglobin (Hb), prealbumin (PA), inflammatory markersprocalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), intestinal mucosal barrier function diamine oxidase (DAO), intestinal fatty acid-binding protein (I-FABP), D-lactic acid (D-LA), and intestinal bacterial counts were compared between the two groups. Results After intervention, BMI and total calorie, intake of fat, carbohydrate, and protein were higher in both groups compared with before intervention, and were higher in the combination group than in the dietary fiber group (P<0.05). After intervention, ALB, Hb, and PA levels were higher in both groups compared with before intervention, and were higher in the combination group than in the dietary fiber group (P<0.05). After intervention, PCT, CRP, and TNF-α levels were lower in both groups compared with before intervention, and were lower in the combination group than in the dietary fiber group (P<0.05). After intervention,D-LA levels were higher, and the DAO and I-FABP levels were lower in both groups compared with before intervention(P<0.05). D-LA levels were higher, while DAO and I-FABP levels were lower in the combination group compared with the dietary fiber group (P<0.05). After intervention, the number of Escherichia coli and Enterococci were lower in the combination group than in the dietary fiber group, while the number of Lactobacilli, Bifidobacteria, and Bacteroides were higher (P<0.05). There were no statistically significant differences in the total incidence of adverse reactions or edema status after intervention between the two groups (P>0.05). Conclusion Microecological agents combined with dietary fiber exhibit significant efficacy in the treatment of COPD, which can stabilize the intestinal microbial community, reduce inflammatory responses, and improve nutritional status.