Objective To evaluate the value of intravenous anesthesia with remimazolam or propofol combined with alfentanil in painless gastrointestinal endoscopy. Methods A total of 100 patients who underwent painless gastrointestinal endoscopy at the First Hospital of Danjiangkou City, Hubei Province were randomly selected from January 2023 to January 2025. According to anesthesia regimens, they were divided into two groups, with 50 cases in each group. The control group was given intravenous anesthesia with propofol combined with alfentanil, while the observation group was administered intravenous anesthesia with remimazolam combined with alfentanil. The vital signs [systolic blood pressure （SBP）, diastolic blood pressure （DBP）, heart rate （HR）, and blood oxygen saturation （SpO₂）], clinical indicators （anesthesia induction time, examination time, and awakening time）, and adverse reactions were compared between the two groups. Results After implementing different intravenous anesthesia regimens, the SBP, DBP, and HR values at 5 min of examination （T2） and at the end of examination （T3）, as well as the SpO₂ at T2, were more stable in the observation group than those in the control group. The anesthesia induction time, examination time, and awakening time were shorter, and the overall incidence of adverse reactions was lower in the observation group than in the control group （P<0.05）. Conclusion For painless gastrointestinal endoscopy, the use of remimazolam combined with alfentanil for intravenous anesthesia has a high application value and is worth promoting.