Laparoscopic cholecystectomy (LC) is a common surgical procedure for the removal of the gallbladder. Effective anesthesia is crucial for ensuring patient comfort and safety during LC. Dexmedetomidine, a selective α2-adrenergic agonist, is widely used as an adjunct to anesthesia due to its sedative and analgesic properties. Nalbuphine, a synthetic opioid analgesic, is also employed for pain management during various surgical procedures. This study aimed to determine the anesthesia effects of dexmedetomidine combined with nalbuphine on patients undergoing LC and its impact on their nutritional status. The clinical records of 100 patients who underwent LC at Wuhan No.1 Hospital between January 2021 and January 2022 were analyzed retrospectively. Forty-six patients who received intravenous dexmedetomidine (0.4 µg/kg) were assigned to the control group, while fifty-four patients who received intravenous nalbuphine (0.2 mg/kg) and dexmedetomidine (0.4 µg/kg) were assigned to the study group. The outcomes compared between the two groups included heart rate (HR), mean arterial pressure (MAP), Riker sedation-agitation scale (RSAS) scores, visual analogue scale (VAS) scores, duration of operation, awakening time from anesthesia, extubation time, adverse reactions, and nutrition-related indicators before and after surgery. There were no significant differences in MAP between the groups at the same time point (p > 0.05). However, at T1 and T3, the study group had significantly lower HR compared to the control group (p < 0.05), with no significant differences in HR at other time points (p > 0.05). The study group exhibited significantly lower RSAS scores compared to the control group (p < 0.01). No significant differences were observed between the groups in terms of duration of operation, awakening time from anesthesia, and extubation time (p > 0.05). At 6 hours post-operation, there were no significant differences in VAS scores between the groups (p > 0.05), but at 12, 24, and 48 hours post-operation, the study group had significantly lower VAS scores compared to the control group (p < 0.0001). No significant inter-group difference was observed in the total incidence of adverse reactions (p = 0.180). Additionally, one week after surgery, the study group exhibited significantly higher levels of albumin, prealbumin, transferrin, and total protein compared to the control group (p < 0.0001). Dexmedetomidine combined with nalbuphine provides a superior anesthetic effect compared to dexmedetomidine alone in patients undergoing LC. This combination effectively controls hemodynamic fluctuations during the recovery period and reduces agitation without affecting the awakening time from anesthesia. These findings suggest that this combination is beneficial and worth promoting.