Objectives Currently, there is a paucity of optimal treatment methods for ischemic stroke. This study conducted a meta-analysis of the application value of indobufen combined with clopidogrel in the field of ischemic stroke. Methods The randomized controlled trials of indobufen combined with/without clopidogrel for the treatment of ischemic stroke were retrieved in Cochrane Library, PubMed, and CNKI from the establishment time of database to November 28, 2023. Cochrane risk-of-bias tool and Review Manager software were used for study quality evaluation and meta-analysis, respectively. Results A total of 5 studies were ultimately included, published from 2021 to 2023, with a total of 408 patients. The meta-analysis results showed that the intervention group had a higher effective rate in treating stroke than the control group, with statistically significant difference (94.25% vs 75.29%, relative risk = 1.25, 95% confidence interval [CI] [1.14, 1.37], P < 0.00001), and there was no significant heterogeneity among the studies (P = 0.64, I-2 = 0%). In addition, the meta-analysis results indicated that indobufen combined with clopidogrel decreased National Institutes of Health Stroke Scale score (mean difference [MD] = -3.52, 95% CI [-5.7, -1.35], P = 0.001), fibrinogen (MD = -0.65, 95% CI [-1.1, -0.2], P = 0.004), platelet aggregation (MD = -5.84, 95% CI [-6.96, -4.73], P < 0.00001), whole blood low shear viscosity (MD = -4.38, 95% CI [-4.81, -3.94], P < 0.00001), and whole blood high shear viscosity (MD = -0.96, 95% CI [-1.19, -0.73], P < 0.00001) and elevated thrombin time (MD = 0.42, 95% CI [0.09, 0.74], P = 0.01), but had no statistical effects on activated partial thromboplastin time and adverse reactions. Conclusion The dual antiplatelet therapy regimen using indobufen and clopidogrel is suitable for the treatment of ischemic stroke, which can effectively alleviate neurological damage and inhibit cerebral thrombogenesis.