This systematic review examines the potential association between semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, and the development of non-arteritic anterior ischemic optic neuropathy (NAION). Nine studies were included, consisting of retrospective cohort analyses, case series, and pharmacovigilance reports. Findings across the literature were inconsistent, with some studies reporting an increased risk while others found no significant association. Variations in study design, diagnostic criteria, and population characteristics limited comparability and prevented meta-analysis. Overall, the absolute risk appears to be low, and the therapeutic benefits of semaglutide in managing type 2 diabetes and obesity are likely to outweigh potential ocular concerns for most patients. Clinicians should exercise caution in individuals with predisposing ocular risk factors, such as small Bruch's membrane opening (BMO), optic disc drusen (ODD), or otherwise crowded optic nerve heads. Further prospective studies with rigorous ophthalmologic evaluation are needed to clarify any causal relationship.