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Objectives. Peripheral artery disease (PAD) in diabetic populations is a vital chronic disease all over the world due to its high morbidity and mortality. It is important to find early simple screening biomarkers and find residual risk factors that may provide a new target for prevention and treatment of PAD in diabetic patients besides traditional cardiometabolic risk factors. Methods. We performed a cross-sectional retrospective study, and a total of 1671 T2DM participants were recruited. Receiver operating characteristic analysis, stepwise logistic regression analysis, points score system, and decision curve analysis were performed to assess the risk factors for PAD. Results. The prevalence of PAD in the study was 7.18% (n = 120). Compared to the participants with the lowest quartile of cystatin C (CysC), the risk of developing PAD in participants with the highest quartile of CysC increased 6.339-fold. The CysC was the superior indicators to distinguish participants with PAD from those without PAD, with an AUC of 0.716. Stepwise logistic regression analysis showed that CysC was independent risk factor for PAD besides traditional risk factors. Combined exposure to these traditional risk factors and CysC was associated with a stepwise increase in the risk of developing PAD and even increased 11.976-fold in participants with the highest quintiles of combined exposure score (CES) based on traditional risk factors and CysC compared to the participants with the lowest quintiles of CES. Conclusions. CysC was associated with PAD independent of potential risk factors in diabetic populations. The CysC was a reliable marker for the early screening of PAD in diabetic patients besides traditional cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]