Objective: Astragali Radix (AR,
Huangqi in Chinese) has a
neuroprotective effect on
cerebral infarction (CI). In order to explore the biological basis and therapeutic mechanism of AR in CI, a double-blind randomized controlled trial was established in this study, and proteomics analysis was carried out on serum samples of patients. Methods: The patients were divided into the AR group (n = 35) and the control group (
n = 30). The curative effect was evaluated by the
traditional Chinese medicine (TCM) syndrome score and clinical indicators, and the serum of the two groups was analyzed by proteomics. Based on bioinformatics analysis methods, the changes in differential
proteins between two groups of samples were explored, and the key
proteins were validated through
enzyme-linked
immunosorbent assay (ELISA). Results: The results of this study showed that the scores of deficiency of vital energy (DVE), blood stasis (BS), and NIH
Stroke Scale (NIHSS) decreased significantly (p < 0.05), while the scores of the Barthel Index (BI) increased, indicating that AR could significantly improve the symptoms of CI patients. In addition, we found that compared with the control group, AR upregulated 43
proteins and downregulated 20
proteins, especially focusing on anti-
atherosclerosis and
neuroprotective effects. Moreover, ELISA indicated the levels of
IL-6, TNF-α,
VCAM-1, MCP-1, and
ICAM-1 were significantly decreased in the serum of the AR group (p < 0.05, p < 0.01). Conclusion: This study found that AR can significantly recover the clinical symptoms of CI. Serum proteomics research results show that AR may act on
IL-6, TNF-α,
VCAM-1, MCP-1, and
ICAM-1, and play anti-
atherosclerosis and neuroprotective roles. Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT02846207].