Objective To investigate the changes in the intestinal neurotransmitters, mental and psychological state, and quality of life in the elderly patients with slow-transit constipation (STC). Methods A total of 115 elderly STC patients in the Department of Anorectal Surgery of Guang′an Hospital of West China Hospital affiliated to Sichuan University from December 2020 to December 2022 were included in the observation group, and 90 age-matched elderly individuals without gastrointestinal diseases in the Physical Examination Department during the same period were enrolled as the control group. Peripheral venous blood was collected from the subjects to detect the levels of intestinal neurotransmitters including serum substance P (SP), nitric oxide (NO), and 5-hydroxytryptophan (5-HT). The symptom check-list 90 (SCL-90) was used to assess the mental and psychological status of the subjects, and MOS short-form-36 health survey (SF-36) was used to assess their quality of life. The patients in the observation group were given mental and psychological intervention for 6 months, and the serum intestinal neurotransmitters, SCL-90 scores and SF-36 scores were evaluated before and after the intervention. SPSS 20.0 was used for data processing and analysis. Pearson correlation coefficient was used to analyze the correlation between levels of serum neurotransmitters and SCL-90 dimensions in the elderly STC patients. Results The levels of serum SP and 5-HT in the observation group were significantly lower than those in the control group, the NO level was significantly higher than that in the control group, and the differences were statistically significant (P<0.05). The scores for somatization, interpersonal sensitivity, depression and anxiety and total score on SCL-90 in the observation group were significantly higher than the control group, the scores for RP, GH, VT and MH and total score on SF-36 were significantly lower than those in the control group, and the diffe-rences were statistically significant (P<0.05). Pearson correlation analysis indicated that serum SP in the observation group was negatively correlated with scores for somatization, interpersonal sensitivity, and anxiety of SCL-90 (r=-0.243, -0.276, -0.311; P<0.05), that serum NO level was positively correlated with scores for somatization and anxiety (r=0.247,0.283; P<0.05), and that serum 5-HT level was negatively correlated with interpersonal sensitivity and anxiety (r=-0.369, -0.363; P<0.05). After mental and psychological intervention, the levels of serum SP and 5-HT in the observation group increased significantly, the serum NO level decreased significantly, and the average SCL-90 score decreased significantly, and the total SF-36 score increased significantly (P<0.05 for all). Conclusion The quality of life in the elderly STC patients declined significantly compared with that of the control group without gastrointestinal diseases, and the mental and psychological disorders worsen, featuring decreased secretions of intestinal excitatory transmitters and increased secretion of inhibitory transmitters. There is a correlation between serum neurotransmitters levels and mental and psychological disorders in the elderly STC patients. Adjusting the patient′s mental and psychological status can improve the abnormal levels of intestinal neurotransmitters and improve the quality of life of the patient.