Background Patients with diabetes are at a high risk for perioperative ischemic stroke (PIS). The use of biomarkers to identify high-risk patients and predict PIS may provide considerable reference value in clinical decision-making. The aspartate transaminase/alanine transaminase ratio (De Ritis ratio) has been proven to be associated with specific diabetic complications. However, the association between the De Ritis ratio and PIS has not been evaluated in this population. This retrospective cohort study aimed to evaluate the association between the preoperative De Ritis ratio and PIS in patients with type 2 diabetes undergoing noncardiovascular surgery. Methods Data from surgical patients were collected from January 2008 to August 2019. A total of 27,643 patients with type 2 diabetes mellitus (DM) undergoing noncardiovascular surgery under general anesthesia were screened. The optimal De Ritis ratio cutoff value was identified using the receiver operating characteristic (ROC) curve. Logistic regression models were used to evaluate the association between the preoperative De Ritis ratio and PIS. Propensity score matching (PSM), sensitivity analyses, and subgroup analyses were performed to further validate the robustness of this association. Results A total of 151 patients experienced PIS. A De Ritis ratio >= 1.04 was associated with an elevated risk of PIS after adjusting for baseline characteristics (OR [95% CI]: 2.25 [1.59-3.21]; p < 0.001), intraoperative parameters (2.50 [1.80-3.49]; p < 0.001), and all confounding variables (2.29 [1.61-3.29]; p < 0.001). In the propensity score-matched cohort, the association between the De Ritis ratio and PIS remained significant (2.04 [1.38-3.05]; p < 0.001). These associations were also consistently maintained in the sensitivity and subgroup analyses. Conclusions An elevated De Ritis ratio is strongly associated with a higher risk of PIS in patients with type 2 DM undergoing noncardiovascular surgery. This may provide additional information on PIS risk assessment in patients with type 2 DM undergoing noncardiovascular surgery.