Objective To investigate the impact of closed negative pressure drainage in combination with Ilizarov transverse tibial bone transport on oxidative stress and inflammatory response in patients with severe diabetic foot. Methods A total of 60 patients with severe diabetic foot who were admitted to the hospital from July 2019 to March 2023 were recruited as the research subjects. These patients were randomly allocated into a control group （n = 30） and an observation group （n = 30）. The control group received Ilizarov tibial transverse bone transport alone， whereas the observation group was treated with closed negative pressure drainage in conjunction with Ilizarov tibial transverse bone transport. The following parameters were compared between the two groups of patients： the reduction rate of wound size， the healing rate， growth factors ［Epidermal Growth Factor （EGF）， Transforming Growth Factor （TGF）， Vascular Endothelial Growth Factor （VEGF）］， oxidative stress indicators ［Advanced Protein Oxidation Products （AOPP）， Malondialdehyde （MDA）， Superoxide Dismutase （SOD）］， inflammatory factors ［Procalcitonin （PCT）， Interleukin-18 （IL-18）， C-reactive Protein （CRP）］， adverse reactions， and the amputation rate. Results The shrinkage rate and healing rate of patients in the observation group were both significantly higher than those in the control group （P < 0.05）. Post-treatment， the improvement in growth factor levels， including EGF， TGF， and VEGF， in the observation group was more pronounced compared to that in the control group （P < 0.05）. Regarding serum AOPP， MDA， and SOD levels， the improvement in the observation group was superior to that in the control group （P < 0.05）. Moreover， the improvement in inflammatory factor levels such as serum PCT， IL-18， and CRP in the observation group was more notable than that in the control group （P < 0.05）. The incidence of adverse reactions such as redness， swelling， pain， and bleeding in the observation group was 6.67%. When compared with the incidence of 11.67% in the control group， no statistically significant difference was observed （P > 0.05）. The amputation rate of patients in the observation group was 3.33%， which was significantly lower than 23.33% in the control group （P < 0.05）. Conclusions Closed negative pressure drainage combined with Ilizarov tibial transverse bone transport demonstrates better efficacy in the treatment of severe diabetic foot. This treatment modality can effectively promote wound healing， enhance oxidative stress regulation， and inhibit the inflammatory response， presenting a relatively high safety profile. Therefore， the application of closed negative pressure drainage combined with Ilizarov tibial transverse bone transport in the treatment of severe diabetic foot merits clinical reference and promotion.