Background <p>Proliferative diabetic retinopathy (PDR) is a sight-threatening complication of type 2 diabetes mellitus (T2DM), with limited tools available for early prediction. Serum creatinine, a marker of kidney function, may reflect shared microvascular pathology between diabetic nephropathy and retinopathy. However, its role in predicting PDR remains unclear. This review assessed the association between serum creatinine levels and the presence of PDR among patients with T2DM.</p> Methods <p>This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD42024595835). A comprehensive search was conducted in PubMed, Embase, and Web of Science up to October 3, 2024. Observational studies reporting serum creatinine levels in patients with PDR versus non-proliferative diabetic retinopathy (NPDR) or no diabetic retinopathy (non-DR) were included. Standardized mean differences (SMDs) were pooled using a random-effects model. Heterogeneity was assessed with the I² statistic, and sensitivity analyses, meta-regression, and publication bias assessments were performed.</p> Results <p>Eighteen studies involving 25,034 individuals were included. Serum creatinine levels were significantly higher in patients with PDR compared with non-DR (SMD, 0.97; 95% CI, 0.61–1.33; I² = 95.7%) and NPDR (SMD, 0.46; 95% CI, 0.15–0.77; I² = 82.7%). Sensitivity analyses confirmed the robustness of these findings. Meta-regression revealed no significant influence of HbA1c or diabetes duration on effect sizes. The association persisted despite high heterogeneity and potential publication bias.</p> Conclusion <p>Elevated serum creatinine levels are significantly associated with the presence of PDR in patients with T2DM. Although creatinine may serve as a potential biomarker for identifying individuals at risk of PDR progression, further prospective, standardized studies are needed to validate its clinical utility.</p>