Panax notoginseng saponins (PNS), the primary bioactive constituents of the traditional medicinal herb P. notoginseng (Sanqi), have demonstrated antiplatelet properties and the enhancement of functional recovery in patients with ischemic stroke (IS). The potential of PNS as a therapeutic agent for IS has garnered considerable interest in recent years.This study conducted a network meta-analysis (NMA) to provide evidence to indicate the efficacy and safety of PNS and other antiplatelet agents in patients with IS, aiming to determine whether PNS alone or in combination with antiplatelet therapy is more effective than conventional antiplatelet treatments in reducing disability rates.We systematically searched the PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Data, and SinoMed databases to identify eligible RCTs published from inception until 1 December 2023. The primary outcome was the proportion of patients with favorable functional outcome, defined as a modified Rankin scale (mRS) score ≤2 at 90 days. Secondary outcomes included changes in the NIHSS score, changes in the Barthel index (BI), and the occurrence of adverse effects.Fifty eligible studies involving 18,424 patients were included in this NMA. These therapies were included in the studies involving PNS and seven antiplatelet agents. PNS plus aspirin was associated with a higher improvement in mRS compared with clopidogrel plus aspirin (RR: 1.08, 95 % CI: 1.04 to1.12), indobufen (RR: 1.09, 95 % CI: 1.05 to 1.13) and aspirin (RR: 1.08, 95 % CI: 1.05 to 1.12). The surface under the cumulative ranking curve (SUCRA) probability of PNS plus aspirin ranked fourth (57.2 %) in terms of mRS. PNS plus aspirin leads to more decreases in post-treatment NIHSS score change than clopidogrel (mean difference [MD]: -3.31, 95 % CI: -6.51 to -0.11) and aspirin (MD: -3.17, 95 % CI: -5.08 to -1.27). However, PNS plus aspirin was associated with a lower increase in post-treatment BI score than tirofiban plus aspirin plus clopidogrel (MD: -21.47, 95 % CI: -39.96 to -2.98) and ozagrel plus aspirin (MD: -23.82, 95 % CI: -40.79 to -6.84). No significant differences were observed between the different treatment alternatives in terms of adverse events.Overall, our study indicates that initiating PNS plus aspirin therapy within 14 days of symptom onset, is associated with favorable functional outcomes in patients with IS compared with therapy comprising clopidogrel plus aspirin, indobufen, or aspirin alone. As such, PNS plus aspirin presents a potentially viable approach for the clinical treatment of IS, thereby contributing to a reduction in patient disability.Copyright © 2025 Elsevier B.V. All rights reserved.