Although acute minor stroke often presents with mild symptoms, such as unilateral limb weakness, mild aphasia, dizziness or mild cognitive impairment, untreated outcomes could be poor, and optimal treatment methods are still debated. We aimed to identify the optimum treatment for minor strokes with a network meta-analysis.Studies from Embase, Ovid, and Cochrane Library were considered. Randomized controlled trials and prospective cohort studies with ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) no more than five, explicit intravenous thrombolysis or antiplatelet therapy were included. Efficacy outcome was measured by three-month modified Rankin scale (mRS), with primary outcome defined as mRS 0-1 and secondary outcome as mRS 0-2. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at three months.Nine studies encompassing 10,665 patients were meta-analyzed. Aspirin plus clopidogrel (n=4,283) was more strongly associated with primary outcome than aspirin (n=2,128, OR 1.26, 95%CI 1.04-1.54) and rt-PA (n=1,840, OR 1.23, 95%CI 1.00-1.50). Aspirin plus clopidogrel (n=3,933) also had a lower sICH risk than rt-PA (n=2,538, OR 0.11, 95%CI 0.04-0.30) and tenecteplase (n=194, OR 0.15, 95%CI 0.03-0.68), as well as a lower mortality than aspirin alone (n=830, OR 0.27, 95%CI 0.10-0.71). Patients treated with aspirin (n=815) also had a lower sICH risk than rt-PA (n=2538, OR 0.20, 95%CI 0.04-0.95).Dual antiplatelet therapy based on aspirin and clopidogrel offers balanced efficacy and safety, positioning it as a potentially optimal treatment for minor stroke. rt-PA showed comparable efficacy, while its associated risks were more pronounced.Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.