To analyze the application effect of sufentanil combined with dexmedetomidine for conscious sedation in plastic surgery. Methods A total of 70 patients undergoing plastic surgery in Xinjie Town Health Center of Dongtai City from January 2020 to December 2022 were selected and randomly divided into control group and observation group, with 35 patients in each group. The control group was treated with sufentanil alone, and the observation group was treated with sufentanil combined with dexmedetomidine. The levels of Cor, HR, NE, MAP and pain mediators were compared between the two groups. Results At T0, there was no significant difference in the levels of Cor, HR, NE and MAP between the two groups (P >0.05). At T1-T3, the levels of Cor, HR and NE in the observation group were lower than those in the control group (P <0.05), and the level of MAP was higher than that in the control group (P <0.05). At 24 h after operation, the levels of serum SP, 5-HT and PGE2 in the two groups were higher than those before anesthesia induction (P <0.05), and the levels of serum SP, 5-HT and PGE2 in the observation group were lower than those in the control group (P <0.05). Conclusion Sufentanil combined with dexmedetomidine for conscious sedation has a good application effect in plastic surgery, which can effectively improve the levels of Cor, HR, NE and MAP and the level of pain mediators.