Objective: To comparatively analyze the effects of the opioid drugs nalbuphine and butorphanol on respiratory function and sedation status when used for postoperative analgesia, providing a basis for the rational selection of clinical postoperative analgesics. Methods: A total of 520 patients who required analgesic treatment after surgical procedures at our hospital from October 2024 to October 2025 were selected and divided into an observation group (nalbuphine group, n = 300) and a control group (butorphanol group, n = 220) based on analgesic choice. The observation group received intravenous patient-controlled analgesia with nalbuphine postoperatively, while the control group received intravenous patient-controlled analgesia with butorphanol. Respiratory function indicators (respiratory rate [RR], blood oxygen saturation [SpO₂], tidal volume [VT]) and sedation scores (Ramsay score) were observed and recorded at 1 h, 6 h, 12 h, and 24 h postoperatively in both groups. Additionally, the incidence of adverse reactions and analgesic efficacy (VAS score) within 24 h postoperatively was statistically analyzed. Results: There was no statistically significant difference in VAS scores between the two groups at each postoperative time point (all P > 0.05). At 1 h, 6 h, 12 h, and 24 h postoperatively, the RR in the observation group was lower than that in the control group, while VT and SpO₂ were higher in the observation group (all P < 0.05). The Ramsay scores at 1 h, 6 h, 12 h, and 24 h postoperatively in the observation group were lower than those in the control group (all P < 0.001). The rate of moderate sedation in the observation group was higher than that in the control group, while the incidence of excessive sedation was lower in the observation group (all P < 0.05). The overall incidence of adverse reactions within 24 h postoperatively in the observation group was lower than that in the control group (P < 0.01). Conclusion: Both nalbuphine and butorphanol can achieve ideal analgesic effects for postoperative pain relief, but nalbuphine has a lesser impact on patients’ postoperative respiratory function, induces a more moderate sedative state, has a lower incidence of adverse reactions, offers superior safety, and is more suitable as one of the preferred opioid drugs for postoperative analgesia.