Objective To investigate the effect of vacuum sealing drainage(VSD) combined with hydrogel dressing on wound healing and inflammatory level in patients with skin defect of limbs. Methods From April 2022 to June 2023, 84 patients with skin defect of limbstreated in Huanghua People's Hospital were selected as the observation objects. According to the order of establishing medical records in the hospital, the patients were divided into control group and experimental group, with 42patients in each group. The control group was given hydrogel dressing intervention, while the experimental group was given hydrogel dressing combined with VSD technology intervention. The recovery, inflammation levels [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8)] and clinical efficacy were compared between the two groups. Results There was no significant difference in the number of postoperative dressing changes between the two groups (P >0.05). The wound healing time and fibrous connective tissue growth time in the experimental group were shorter than those in the control group, and the flap formation rate was higher than that in the control group (P <0.05). The levels of IL-6, TNF-α and IL-8 in the two groups after operation were lower than those before operation, and those in the experimental group were lower than those in the control group (P <0.05). The total effective rate of treatment in the experimental group was 95.24%, which was higher than 80.95% of the control group (P <0.05). Conclusion The combined intervention of VSD technology and hydrogel dressing can effectively promote the rapid healing of wounds in patients with skin defect of limbs, enhance the survival rate of wound flaps, reduce the inflammatory response of wounds and improve the clinical treatment effect.