Background <p>Gastroscopy is a common medical procedure, but the insertion of the endoscope often causes significant discomfort and anxiety in patients, necessitating effective sedation strategies. Traditional sedatives, such as propofol, are widely used for procedural sedation but can lead to adverse effects, including respiratory depression and cardiovascular instability at higher doses. Oliceridine, a novel opioid analgesic, has emerged as a potential alternative due to its biased agonist properties, which may provide effective analgesia with a more favorable side effect profile. The potential for its combination with propofol warrants further investigation.</p> Methods <p>The ED₉₀ and ED₉₉ were calculated using a biased coin design and central ordered regression. Measurements: The primary outcome measure was the occurrence of body movements or coughing responses during gastroscopy.</p> Results <p>A total of 49 patients were included in this study, with anesthesia successfully achieved in 45 cases and failed in 4 cases. The calculated ED₉₀ and ED₉₉ for Oliceridine combined with Propofol to suppress the response during gastroscopy were22.5 and 23.8&#xa0;µg·kg^− 1, respectively.</p> Conclusions <p>The combination of 2&#xa0;mg·kg^− 1 Propofol and 23.8&#xa0;µg·kg^− 1 Oliceridine is effective in suppressing the responses during the gastroscopy procedure.</p> Trial registration <p>The study was registered in the Chinese Clinical Trial Registry (ChiCTR2400092318) on November 14, 2024.</p>