Diabetic foot ulcer (DFU) is globally a major health burden predisposing to limb amputation. Among the various treatment modalities, platelet-rich plasma (PRP) is emerging as a promising agent. It stimulates wound healing by providing a higher concentration of essential growth factors locally. Though the role of PRP in DFU healing is established, still the route of administration with maximal efficacy is yet to be defined. Our study aims to evaluate the efficacy of autologous PRP in the treatment of diabetic ulcers and compare the effect of topical and perilesional injections of PRP in DFU healing. We conducted a single-centre, prospective, interventional study on 60 patients with DFU, in 2 groups of 30 patients each. They were treated with freshly prepared autologous PRP injection perilesionally and topically respectively, once a week for 4 weeks. Ulcer size was assessed, using "imito-measure" software at presentation and 2, 4, 8, and 12 weeks post-therapy. Serum MMP-9 levels were assessed in both groups, pretreatment and post-treatment. For statistical analysis, SPSS software V-23 was used. On assessment, both groups had comparable baseline characteristics, Wagner's grading, and glycemic indices. The percentage reduction in the size of the wound at 2 weeks, 1 month, 2 months, and 3 months was greater in the perilesional group as compared to the topical PRP group.