Chronic kidney disease (CKD) is a progressive condition that results in a decline in kidney function over time. There are several conditions that increase the likelihood of developing CKD, particularly diabetes and hypertension. CKD increases the risk of mortality and has a detrimental impact on quality of life (QoL). Strategies for managing CKD include controlling cardiovascular risk factors and treating complications of CKD. There is an ever-increasing role of pharmacists in managing CKD, from the optimization of risk factors to patient education. However, currently, there is a lack of data on the effect pharmacist-led interventions have on the clinical, economic, and humanistic outcomes. This protocol, in adherence to PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) standards, describes a prospective systematic review and meta-analysis of randomized controlled trials, where any intervention led by a pharmacist in CKD is used. Comparison groups will consist of usual care or non-pharmacist-led interventions. Literature searches will be conducted in the following databases: MEDLINE, Scopus, and Web of Science. Data pertaining to clinical (e.g., mortality), economic (e.g., healthcare-associated costs), and humanistic (e.g., QoL) outcomes will be extracted. Risk of bias will be assessed using the United States National Heart Lung and Blood Institute quality assessment tool for controlled intervention studies. A meta-analysis will be conducted to synthesize appropriate comparable outcomes. The findings of this review will be published in a peer-reviewed journal, where the results will be presented in lay language with appropriate infographics online and via social media. The findings of this review can identify gaps in the literature concerning optimizing pharmacist-led interventions in improving outcomes. In addition, this review will establish the importance of pharmacists in managing CKD patients, and whether this may result in their increased incorporation in multidisciplinary teams.