Abstract：Objective：To observe the clinical efficacy of acupuncture for post-stroke depression （PSD） under the guidance of the "brain-gut axis" theory. Methods： A total of 78 PSD patients hospitalized in the First Affiliated Hospital of Wenzhou Medical University from January 2023 to December 2025 were enrolled. They were divided into a treatment group and a control group using the random number table method， with 39 cases in each group. During treatment，3 cases dropped out from each group，finally，36 cases in each group completed the study. On the basis of conventional treatment， the treatment group received acupuncture， while the control group received Paroxetine Hydrochloride Tablets. After four weeks of treatment， changes in depression [Hamilton Depression Scale （HAMD） score， Self-Rating Depression Scale （SDS） score]， activities of daily living [modified Barthel Index （BI） score]， neurological deficit [National Institutes of Health Stroke Scale （NIHSS） score]，nutrition [Body Mass Index（ BMI），red blood cell count， hemoglobin， serum albumin， and serum prealbumin]， and levels of inflammatory factors [interleukin-1β （IL-1β），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），nuclear factor-κB （NF-κB）] were compared in the two groups. Results： After treatment， the total effective rate was 94.44% （34/36） in the treatment group and 72.22% （26/36） in the control group，and the difference between the two groups was statistically significant（ P＜0.05）. After treatment，the HAMD and SDS scores in both groups decreased compared with those before treatment （P＜0.05）， and the HAMD and SDS scores in the treatment group were lower than those in the control group （P＜0.05）. After treatment， the NIHSS scores in both groups decreased compared with those before treatment （P＜0.05）， while the BI scores increased compared with those before treatment （P＜0.05）； the NIHSS score in the treatment group was lower than that in the control group （P＜0.05），and the BI score was higher than that in the control group （P＜0.05）. After treatment， the nutritional indicators including BMI， red blood cell count， hemoglobin，serum albumin，and serum prealbumin levels in the treatment group increased compared with those before treatment and were higher than those in the control group，with statistically significant differences （P＜0.05）；while there were no statistically significant differences in the above indicators in the control group before and after treatment （P＞0.05）. After treatment， the levels of IL-1β， IL-6， TNF-α， and NF-κB in both groups decreased compared with those before treatment （P＜0.05）， and the levels of IL-1β， IL-6， TNF- α， and NF- κB in the treatment group were lower than those in the control group （P＜0.05）. The incidence of adverse reactions was 8.33% （3/36） in the treatment group and 13.88% （5/36） in the control group， and the difference between the two groups was not statistically significant （P＞0.05）. Conclusion： Acupuncture in the treatment of PSD under the guidance of the "brain-gut axis" theory can enhance clinical efficacy， alleviate depressive symptoms， reduce neurological deficits，improve nutrition and activities of daily living in patients，with favorable safety.