Abstract： Objective： To systematically evaluate the clinical effect and safety of Naomaili Granules combined with conventional treatment for ischemic stroke （IS）. Methods：Computer-based retrieval was conducted in PubMed， EMBASE，Cochrane Library，China Biology Medicine disc（ CBM），China National Knowledge Infrastructure（ CNKI）， Wanfang database， VIP database， and National Excellent Master's and Doctoral Dissertations database from their establishment to August 1， 2025. Randomized controlled trials （RCTs） on Naomaili Granules combined with conventional treatment for IS were included. RevMan 5.4 software was used for meta-analysis of clinical effect and safety indicators， and TSA 0.9.5.10 Beta software was applied for trial sequential analysis （TSA） of the total effective rate. Results： A total of 19 studies involving 2 014 subjects were included， with 1 015 cases in the trial group and 999 cases in the control group. Meta-analysis showed that： the total effective rate [relative risk （RR）=1.16， 95% confidence interval （CI） （1.11， 1.21）， P＜0.000 01]， Barthel Index （BI） score [mean difference （MD）=12.02， 95%CI（ 9.45，14.60），P＜0.000 01]，and the proportion of patients with modified Rankin Scale（ mRS） score ≤2 [RR= 1.59，95%CI （1.17，2.17），P=0.003] in the trial group were significantly higher than those in the control group. In contrast， the National Institutes of Health Stroke Scale （NIHSS） score [MD=-1.68， 95%CI （-1.91， -1.45）， P＜ 0.000 01]， mRS score [MD=-0.36， 95%CI （-0.50， -0.21）， P＜0.000 01]， total cholesterol （TC） [MD=-0.27， 95%CI （-0.33，-0.21），P＜0.000 01]，triglycerides （TG） [MD=-0.20，95%CI （-0.24，-0.17），P＜0.000 01]， low-density lipoprotein cholesterol （LDL-C） [MD=-0.86， 95%CI （-0.93， -0.78）， P＜0.000 01]， interleukin- 6 （IL-6） [MD=-13.20， 95%CI （-17.07， -9.23）， P＜0.000 01]， tumor necrosis factor-α （TNF-α） [MD=-8.08， 95%CI（ -12.11， -4.05） ， P＜0.000 01]， and high-sensitivity C-reactive protein （hs-CRP） [MD=-3.03， 95%CI （-3.31，-2.74），P＜0.000 01] in the trial group were significantly lower than those in the control group. There was no statistically significant difference in the effective rate of traditional Chinese medicine syndromes， interleukin high-density lipoprotein cholesterol （HDL-C），and incidence of adverse reactions between the two groups （P＞0.05）. TSA results indicated that after including a sufficient sample size， the cumulative Z-value of the total effective rate exceeded both the traditional threshold and the TSA boundary， further confirming the clinical effect of Naomaili Granules combined with conventional treatment for IS. Conclusion： Compared with conventional treatment alone， Naomaili Granules combined with conventional treatment for IS can improve the total effective rate，reduce NIHSS score and disability degree， promote neurological function recovery， regulate blood lipid levels， and inhibit inflammatory responses，without significantly increasing the incidence of adverse reactions.