No study has investigated the role of induced membrane (IM) formation in treating diabetic foot ulcer (DFU). This retrospective study was aimed (1) at evaluating the potential role of a two-staged surgical approach, comprising polymethylmethacrylate (PMMA) implantation and IM formation, in the treatment of DFU and (2) at comparing the results of those with routine wound debridement in patients with DFUs and nonrevascularized peripheral arterial disease (PAD). Fifty patients with infected DFUs who were not candidates for vascular interventions were enrolled between February 2016 and April 2018 and assigned to the PMMA group (n = 28) and conventional group (n = 22). The healing rate, major amputation rate, duration of healing, frequency of debridement procedures, patient survival rate, and reulceration of DFUs were determined. The Mann-Whitney U test, independent sample t-test, and χ2 or Fisher exact test were used in statistical analysis. Overall clinical outcomes were statistically different between the groups (Z = −2.495, P = 0.013). In the PMMA group, 16 patients (57.1%) with intact IM formation achieved ulceration healing at 13.1 ± 3.7 weeks with a mean number of debridements of 1.3 ± 0.4, which were significantly different compared to those values in 5 patients of the conventional group (22.7%, P = 0.014; healing duration: 26.4 ± 7.8 weeks, P = 0.016; mean number of debridements: 3.6 ± 0.5, P ≤ 0.001). At a mean 16.8 ± 4.3-month follow-up, patient survival rates were 92.9% and 68.2% in the PMMA and conventional groups, respectively (P = 0.032). The major amputation rate and reulceration of DFUs were similar between the groups. The two-staged surgical approach is an available, effective modality for improving healing of DFUs. This study provides preliminary information of IM formation followed by PMMA implantation in the management of DFUs in PAD when revascularization is not feasible.