The incidence of post stroke cognitive impairment (PSCI) is high in patients with mild stroke (MIS), and the risk factors and mechanism are uncertain. Increased cystatin C (CysC) levels after stroke may reflect lower glomerular filtration rate (GFR) and renal impairment. Previous studies have suggested endothelial dysfunction (ED) is closely related to renal impairment and cognitive impairment, respectively. We aimed to observe whether lower GFR estimated by CysC after MIS leaded to a high incidence of PSCI, and the role of ED in this process. 256 patients were enrolled in this prospective observational study. Renal function was assessed using GFR estimated by serum CysC. Endothelial function was evaluated by reactive hyperemia index (RHI) which calculated automatically by peripheral arterial tonometry (PAT). The cognitive function at baseline and 3 months was evaluated by MoCA score, and MoCA score ≤ 26 indicates the presence of PSCI. Spearman correlation analysis and linear regression were conducted to explore the factors affecting ED. Univariate and multivariate analysis was used to identify the independent risk factors of PSCI. The receiver operating characteristic (ROC) curve was applied to explore the optimal cutoff value of the independent risk factors levels for predicting PSCI. A total of 141 patients (55.1%) suffered from ED. Multiple linear regression analysis showed that there was a strong linear correlation between eGFRcys and RHI (p < 0.001). At the three-month follow-up, a total of 150 (58.6%) patients had been diagnosed with PSCI. Multivariate logistic regression analysis showed that RHI was an independent factor affecting the occurrence of PSCI (p < 0.05). ROC curve showed that the area under the curve was 0.724, and the optimal cut-off value of RHI was 1.655, with the sensitivity and specificity for PSCI were 72.7% and 73.6%, respectively. The lower eGFRcys level after MIS was significantly associated with ED, and ED may mediate the higher incidence of PSCI at 3 months after MIS.