Chronic obstructive pulmonary disease (COPD) is a major public health concern. Exacerbation of COPD leads to poor health and frequent episodes of increased systemic and airway inflammation. Immunomodulatory drugs have garnered extensive attention because they may reduce the rate of COPD exacerbation. This review aimed to evaluate the efficacy and safety of nemiralisib in COPD patients.Medical databases, including the Cochrane Library, EMBASE, and PubMed, were queried from inception to June 2023 to identify randomized controlled trials (RCTs) on the efficacy of nemiralisib in COPD patients. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Collaboration tool was used to assess the risk of bias of the included RCTs. Two authors independently conducted literature screening and data extraction. Key information from the included studies was extracted, tabulated, and compared using a data extraction table. Moreover, the key characteristics, quality, potential bias, and endpoint outcomes of the included studies were summarized. A meta-analysis was conducted when the study outcomes were sufficiently comparable, and the required data were available for extraction.Initially, 48 references were identified, leading to the inclusion of four trials. No significant difference was found between the nemiralisib and placebo groups in St George's Respiratory Questionnaire score, modified Medical Research Council Dyspnea Scale score, COPD Assessment Test score, time to next on-treatment exacerbation, proportion of patients achieving exacerbation recovery, time to exacerbation recovery, and rescue medication use. Contrastingly, the results demonstrated that nemiralisib may lower oral corticosteroid use during acute exacerbation of COPD. Meanwhile, the efficacy of nemiralisib on the exacerbation rate, as well as several parameters associated with lung function, including forced expiratory volume in 1 second, specific airway conductance, specific imaging airway wall thickness, distal specific imaging airway volume measured at functional residual capacity, specific imaging airway resistance, low attenuation score, and internal airflow lobar distribution in the lower pulmonary region, were conflicting. Attributed to the limited number of included RCTs and insufficient extracted data, it was not feasible to conduct a comprehensive meta-analysis.Because of insufficient data, this systematic review could not make any definitive statement regarding the efficacy of nemiralisib in COPD patients. In terms of safety, nemiralisib was generally well tolerated. Further trials are required to explore the efficacy of this drug.Copyright © 2024 Elsevier Inc. All rights reserved.