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This study aimed to explore the risk of overall extracranial bleeding events with tirofiban in patients with acute ischemic stroke (AIS) and diabetes mellitus and analyze the impact of blood glucose control on this risk. A single-center retrospective cohort study design was used, including 100 patients with AIS and diabetes mellitus admitted between April 2023 and November 2025. Propensity score matching was used to divide patients into the tirofiban group (50 cases) and the control group (50 cases). The primary outcome was the incidence of overall extracranial bleeding events within 7 days after medication administration. Secondary outcomes included types of extracranial bleeding (e.g., gingival bleeding), thrombocytopenia, and neurological function outcomes. Multivariable logistic regression and subgroup analysis were conducted to assess independent risk factors. The incidence of overall extracranial bleeding events in the tirofiban group was 32.0%, significantly higher than the 16.0% in the control group (risk ratio = 2.00, 95% confidence interval = 1.11-3.60, P = .021). Gingival bleeding (10.0% vs 2.0%, P = .047) and thrombocytopenia (10.0% vs 2.0%, P = .047) occurred more frequently in the tirofiban group. Multivariable analysis showed that tirofiban treatment (adjusted odds ratio = 2.45, P = .018) and admission random blood glucose (adjusted odds ratio = 1.22, P = .032) were independent risk factors for overall extracranial bleeding events. Subgroup analysis revealed that in patients with hemoglobin A1c ≥7.5%, the bleeding risk associated with tirofiban was higher (odds ratio = 3.33, 95% confidence interval = 1.05-10.56, P-interaction = .04). In patients with AIS and diabetes mellitus, tirofiban treatment did not significantly increase the risk of intracranial hemorrhage, but it significantly raised the risk of extracranial bleeding events (especially gingival bleeding) and thrombocytopenia. This risk was more pronounced in patients with poor blood glucose control. Comprehensive monitoring of bleeding signs and enhanced glucose management are required in clinical practice.