Objective: To evaluate the therapeutic effects of Huangqi Sijun Decoction on chronic atrophic gastritis (CAG). Methods: Sixty CAG patients hospitalized between January 2020 and December 2022 were selected and randomly divided into two groups using a random number table. The Traditional Chinese Medicine (TCM) group (n = 30) was treated with Huangqi Sijun Decoction, while the Western medicine group (n = 30) received omeprazole. The total effective rate, TCM syndrome scores, and serological indicators were compared. Results: The total effective rate in the TCM group was higher than that in the Western medicine group, while the adverse reaction rate was lower (P < 0.05). Before treatment, there were no significant differences in TCM syndrome scores or serological indicators between the two groups (P > 0.05). After treatment, the TCM group had lower TCM syndrome scores and better serological indicators compared to the Western medicine group (P < 0.05). Conclusion: Huangqi Sijun Decoction can enhance the clinical efficacy of CAG patients, prevent adverse reactions, alleviate TCM symptoms, and regulate specific levels of serological indicators, demonstrating significant therapeutic advantages.