Objective: To study the clinical effect of Mazirenzengye decoction combined with acupuncture at Tianshu point in the treatment of post-stroke constipation. Methods: 102 patients with poststroke constipation admitted to our hospital from March 2022 to May 2024 were selected as the study objects. The patients were divided into control group and observation group by random number table, with 51 cases in each group. The control group was treated with acupuncture at Tianshu point. The observation group was treated with Mazirenzengye decoction combined with acupuncture at Tianshu point. The curative effect, TCM syndrome score, serological index (motilin, 5-hydroxytryptamine) and quality of life of the two groups were analyzed and compared. Results: The effective rate of the observation group was significantly higher than that of the control group (P < 0.05). After treatment, the main disease, concurrent disease and total score of the two groups were significantly lower than before treatment, and the main disease, concurrent disease and total score of the observation group were significantly lower than those of the control group (P < 0.05). After treatment, the levels of serotonin and motilin in both groups were significantly lower than before treatment, and the levels of motilin were significantly higher than before treatment. The levels of motilin and 5-hydroxytryptamine in the observation group were significantly higher than those in the control group (P < 0.05). After treatment, the PAC-QOL score of both groups was significantly lower than that before treatment, and the PAC-QOL score of the observation group was significantly lower than that of the control group (P < 0.05). Conclusion: Mazirenzengye Decoction combined with acupuncture at Tianshu point can improve the symptoms of constipation patients after stroke, improve the clinical efficacy, improve the contents of motilin and 5-hydroxytryptamine, and improve the quality of life.