Many central nervous system (CNS) disorders lack approved treatment options. Previous research demonstrated that peptide CAQK can bind to chondroitin sulfate proteoglycans (CSPGs) in the extracellular matrix of the CNS. In vivo studies have investigated CAQK conjugated to nanoparticles containing therapeutic agents with varying methodologies/outcomes. This paper presents the first systematic review assessing its properties, applications, and outcomes secondary to its use. Following PRISMA guidelines, a comprehensive search was performed across multiple databases. Studies utilizing CAQK as a therapeutic agent/homing molecule in animal/human models were selected. Sixteen studies met the inclusion criteria. Mice and rats were the predominant animal models. All studies except one used CAQK to deliver a therapeutic agent. The reviewed studies mostly included models of brain and spinal cord injuries. Most studies had intravenous administration of CAQK. All studies demonstrated various benefits and that CAQK conjugation facilitated localization to target tissues. No studies directly evaluated the effects of CAQK alone. The data are limited by the heterogeneity in study methodologies and the lack of direct comparison between CAQK and conjugated agents. Overall, these findings present CAQK utilization to deliver a therapeutic agent as a promising targeting strategy in the management of disorders where CSPGs are upregulated.