To analyze the effects of propofol combined with dexmedetomidine used during laparoscopic myomectomy of patients on their postoperative pain and stress response. Methods: 92 patients who wanted laparoscopic myomectomy were randomly assigned to two groups from January 2021 to December 2023. 46 patients in control group received propofol combined with sufentanil for anesthesia maintenance, while 46 patients in observation group received propofol combined with dexmedetomidine for anesthesia maintenance. The postoperative pain degree evaluated by VAS score, the cognitive function evaluated by MMSE score, the levels of stress response of cortisol (Cor) and inflammatory factor of cytokine-6 (IL-6), and  rates of adverse reactions, such as nausea and vomiting, hypoxemia, respiratory depression and restlessness, of the patients were compared between the two groups. Results: The VAS scores of the patients in the observation group at 2 h, 6 h, 12 h and 24 h after operation (2.91±0.52 points, 2.51±0.50 points, 2.06±0.43 points and 1.73±0.35 points) were significantly lower than those (3.59±0.60 points, 3.06±0.57 points, 2.40±0.47 points and 2.10±0.40 points) of the patients in the control group. The MMSE score of the patients in the two groups at 24 h after operation had decreased significantly, and which (27.80±1.11 points) of the patients in the observation group was significantly higher than that (26.74±1.08 points) of the patients in the control group. The serum levels of Cor and IL-6 of the patients in the two groups at 24 h after operation had increased significantly, and which (16.29±3.29 mmol/L and 78.39±6.72 pg/ml) of the patients in the observation group were significantly lower than those (20.46±3.40 mmol/L and 86.35±6.11 pg/ml) of the patients in the control group. The total incidence of adverse reactions (4.4%) of the patients in the observation group was significantly lower than that (17.4%) of the patients in the control group (all P<0.05). Conclusion: The combination of propofol and dexmedetomidine used during laparoscopic myomectomy of the patients has good anesthetic effect, which can reduce the pain degree and cognitive impairment of the patients, improve the stress response indicators and inflammatory factor levels of the patients, and has fewer adverse reactions and better medicine safety.