Objective To investigate the effect of Propofol combined with Dexmedetomidine on stress response in patients undergoing peritoneal surgery under anesthesia. Methods One hundred and six patients admitted to the Affiliated Hospital of Yan'an University undergoing abdominal surgery from February 2015 to February 2017 were divided into two groups according to random number table. In the control group, Propofol was used to maintain anesthesia. In the observation group, Propofol and Dexmedetomidine were used for anesthesia maintenance. The serum levels of A-Ⅱ, NE, COR and E at T0, skin incision (T1), the beginning of surgery 0.5 hours (T2) and before the tube (T3) were compared between two groups. The changes of GSH-PX, LPO and Cu-Zn SOD in both groups before and after extubation were observed. The occurrence of adverse reactions within 24 h after surgery were record in two groups. Results Compared with T0, the serum levels of A-Ⅱ, NE, COR and E increased significantly during T1 to T3(P < 0.05), and the above indexes in the observation group were significantly lower than those in the control group at three time points from T1 to T3(P < 0.05). After extubation, the levels of GSH-PX, Cu-Zn SOD were significantly decreased(P < 0.05), and LPO levels were significantly increased in the two groups (P < 0.05). The levels of GSH-PX, Cu-Zn SOD in the observation group were significantly higher than those in the control group (P < 0.05), and the LPO level was significantly lower than that of the control group (P < 0.05). The incidence of adverse reactions in the observation group was only 5.66% at 24 h after operation, which was significantly lower than that in the control group (18.87%) (P < 0.05). Conclusion Propofol and Dexmedetomidine combined application of anesthesia in patients undergoing abdominal surgery, can effectively inhibit the stress response during surgery, ease intraoperative oxidative damage, has fewer adverse reactions, and has high safety.