Objective: To explore the clinical efficacy and safety of Naomaili granules in the treatment of acute ischemic stroke. Methods: Eighty-eight patients were randomly divided into a treatment group and a control group, with 44 patients in each group. The control group received conventional Western medicine treatment, while the treatment group was additionally administered Naomaili granules at 10g per time, 3 times per day, for 20 days. Neurological function (NIHSS), activities of daily living (BI), inflammatory factors (hs-CRP, IL-6) levels, and adverse reactions were observed before and after treatment. Results: After 20 days of treatment, the NIHSS score of the treatment group decreased from (9.20 ± 2.10) to (5.12 ± 1.30), the BI index increased from (52.30 ± 8.50) to (78.60 ± 9.20), and hs-CRP and IL-6 decreased to (3.12 ± 1.10) mg/L and (18.20 ± 4.20) pg/mL, respectively, all significantly better than the control group (P < 0.01). The incidence of adverse reactions in the treatment group was 4.55%, lower than the 15.91% in the control group (P < 0.05). Conclusion: Naomaili granules can improve neurological function and living ability, reduce inflammatory response, and have good safety in patients with acute ischemic stroke.