Atherosclerosis is the leading cause of cardiovascular disease (CVD), which is one of the most common causes of morbidity and mortality worldwide. Lipid accumulation and inflammation play a crucial role in the pathogenesis of atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging lipid-lowering agent reported as a potential anti-inflammation effect in the prevention of CVD. However, the anti-inflammatory effect is still elusive. Therefore, a systematic review and meta-analysis is needed to analyse the anti-inflammatory effect of PCSK9 inhibitors on atherosclerosis in practice.This protocol was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. We will include double-blind, randomised controlled trials that reported changes in the levels of inflammatory markers, with an intervention arm of PCSK9 inhibitors and a treatment duration of more than 2 weeks. The following databases will be mainly searched from 1 January 2003 to the formal search date: PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials. The primary aim is to assess the effect of PCSK9 inhibitors on inflammatory markers, including circulating inflammatory markers such as C-reactive protein, high-sensitivity C-reactive protein, white cell counts, IL-1β, IL-6 and TNF-α and local inflammatory markers such as the most diseased segment target-to-background ratio of the index vessel in adult patients with atherosclerosis. We will assess the quality of evidence, heterogeneity and report bias following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.Due to the systematic review being based on published studies, no ethics approval is required. The study results will be presented at international conferences and published in a peer-reviewed journal.CRD42022297710.© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.