Aim To investigate the clinical efficacy and preliminary mechanism of Yiqi Huoxue Jiangzhuo decoction combined with butylphthalide in the treatment of transient ischemic attack (TIA). Methods A total of 120 patients with TIA admitted to the First People's Hospital of Nanyang from January 2022 to March 2023 were selected as the research subjects and randomly divided into three groups with 40 cases in each group. The control group 1 was given butylphthalide, the control group 2 was given Yiqi Huoxue Jiangzhuo decoction, and the observation group was given Yiqi Huoxue Jiangzhuo decoctionn combined with butylphthalide for 2 months of treatment. After 2 months of treatment, the clinical efficacy and adverse reaction rate were compared among the three groups. The ABCD2 scores, national institute of health stroke scale (NIHSS) scores, and serum biochemical indicators (soluble CD40 ligand (sCD40L), lipoprotein-associated phospholipase A2 (Lp-PLA2), high-sensitive C-reactive protein (hs-CRP), peripheral blood Kelch-like epichlorohydrin-related protein-1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway-related protein levels (Keap1, Nrf2, ARE) , and hemodynamic indicators (mean blood flow velocity (Vm), mean blood flow volume (Qm), cerebral vascular resistance (R) were compared before treatment and at 1 and 2 months after treatment in the three groups. Results The total clinical efficacy rate in observation group was significantly higher than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, the ABCD2 scores and NIHSS scores in the three groups showed a significant downward trend after 1 month and 2 months of treatment, and the decrease in observation group was larger than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, sCD40L, Lp-PLA2, and hs-CRP in the three groups showed a significant downward trend after 1 month and 2 months of treatment, and the decrease in observation group was larger than that in control group 1 and control group 2 (P＜0.05). Compared with before treatment, Keap1 protein in the three groups showed a significant downward trend after 1 month and 2 months of treatment, and the decrease in observation group was larger than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, the Nrf2 protein and ARE protein in the three groups showed a significant increase trend after 1 month and 2 months of treatment, and the increase amplitude in observation group was larger than that in control group 1 and control group 2 (P＜0.05), but there was no significant difference between the two control groups (P＞0.05). Compared with before treatment, Qm, Vm of the three groups increased and R decreased significantly at 1 month and 2 months after treatment, and the Qm, Vm in observation group were significantly higher than that in control group 1 and control group 2, while R was significantly lower than that in control group 1 and control group 2 (P＜0.05). Conclusion Yiqi Huoxue Jiangzhuo decoction combined with butylphthalide is more effective than butylphthalide and Yiqi Huoxue Jiangzhuo decoction alone in treating TIA, can improve neurological function, cerebral hemodynamics, inhibit inflammatory response, and has a certain degree of safety, and its mechanism of action is related to the regulation of Keap1-Nrf2/ARE signaling pathway.