Objective. To investigate the effect of applying remimazolam combined with esketamine for anesthesia in painless gastroenteroscopy on patients’ circulatory and respiratory function. Method. In this study, 106 patients who had undergone painless gastroenteroscopy in Xinjiang Production and Construction Corps (XPCC) Hospital between July 2021 and January 2022 were selected as study subjects, which were grouped according to the anesthetic drugs used in the surgery and divided into control group (n = 53 cases) and observation group (n = 53 cases), while those who were anesthetized with propofol + sufentanil during the operation were the control group and those who were anesthetized with remimazolam + esketamine were the observation group. To compare the induction time of anesthesia, patient awakening and recovery time of orientation, circulatory and respiratory function, intraoperative adverse effects, and postoperative complications in the two study groups. Results. There was no statistical difference in induction of anesthesia, patient awakening, and recovery time of orientation between the two groups ( P > 0.05 ) and no statistical difference in postoperative complications ( P > 0.05 ). The observation group had a better occurrence of local pain at the injection site, circulatory and respiratory function of patients after anesthesia, and intraoperative adverse reactions than the control group ( P < 0.05 ). Conclusion. Remimazolam combined with esketamine anesthesia has the same advantages of rapid awakening compared with propofol anesthesia. Moreover, it has fewer side effects on patients’ circulatory and respiratory functions with fewer adverse effects, as a suitable anesthetic method for painless gastroenteroscopy.