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Chronic Obstructive Pulmonary disease (COPD) is a chronic and progressive respiratory disorder primarily caused by smoking. It is a leading cause of morbidity, mortality, and hospital admissions world-wide. Acute exacerbation (AECOPD) episodes can be triggered by infection or environmental stressors and are associated with a significant decline in patient pulmonary function as well as low short and long-term survival rates. Current prophylaxis and treatment regimens for AECOPD are of limited benefit. Immunoglobulin therapy is a novel approach to AECOPD patient management but its effectiveness in patient care has not been established and is in need of further study. We will conduct a systematic review and meta-analysis to assess clinical outcomes associated with the administration of intravenous/subcutaneous immunoglobulin (IVIG/SCIG) in the prevention of acute exacerbations of COPD (AECOPD). We will search Embase, Ovid MEDLINE, and Cochrane Central Register of Controlled Trials for randomized and non-randomized studies relevant to this review. As per the PRISMA protocol, retrieved studies will undergo screening and data extraction processes conducted by two independent reviewers. We will report the corresponding relative risk ratios as the primary measure, with 95% confidence intervals (CIs). We will also use a random-effects model to calculate pooled measures for these studies. The risk of bias will be assessed in randomized and nonrandomized trials using the Cochrane Risk of Bias Assessment Tool Version 2 and the ROBINS-I tool, respectively. Our systematic review will provide the current status on the effectiveness of the prophylactic and therapeutic uses of IVIG/SCIG in the management of COPD patients. Results from this review may be applicable to clinical practice and may also lay the foundation for future research in this field.