Background: In this study, the chronic wound healing ability of PLA-based electrospun nanofibers loaded with hyaluronic acid, valsartan, and ascorbic acid is explored. PLA-based scaffolds were fabricated by electrospinning, followed by loading the scaffolds with different concentrations of hyaluronic acid, valsartan, and ascorbic acid hydrogels. The produced formulations were characterized by scanning electron microscopy imaging (SEM), tensile strength testing, Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). An in vitro drug release study was conducted to monitor the release of valsartan from the different formulations. This was followed by exploring the wound healing effects of the scaffolds in alloxan-induced diabetic rats and comparing the wound healing effects with positive and negative controls. Results: The average diameter of the fibers was in the range of 300 to 490 nm with high porosity in the range of 63.90 to 79.44%, offering a large surface area-to-volume ratio, enhanced drug solubility, oxygen permeability, and fluid uptake. The presence of valsartan significantly impacted on the re-epithelization rate. Percentage reepithelization rate was 31.2% ± 1.77% in the absence of treatment. Histologic section of tissue showed skin with underlying loose fibro-collagenous stroma (dermis) containing sebaceous glands and hair follicles for animals treated with VA, VB, VC, and VD. All the scaffolds reduced the number of inflammatory cell infiltrates at the wound site compared to the no treatment and conventionally treated groups. Conventional antibiotic treatment and VD (electrospun biomimetic scaffolds containing ascorbic acid) had % re-epithelization rates of 59.45% ± 1.69% and 62.01% ± 1.68% which were significantly lower than the PLA/HA-valsartan hydrogel scaffolds with VB having the highest % re-epithelization rate of 85.5% ± 1.7% (Figure 4B & 5C). Conclusion: This study explored the use of biomimetic polylactic acid-based electrospun fiber and HA-valsartan hydrogel scaffold incorporating topical angiotensin receptor blockers to successfully accelerate wound healing. The novel PLA-based electrospun fibers loaded with hyaluronic acid-valsartan hydrogels were stable and possessed proven diabetic wound healing property. This was as a result of the known biomimetic effect of the fibers and increased re-epithelization facilitated by the hydrogels containing valsartan.