Purpose <p>Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus, which is marked by dysfunctional angiogenesis, chronic inflammation, and dysregulated extra cellular matrix (ECM) remodeling. Traditional treatments, such as growth factor- and cytokine-mediated therapies, have proven to be ineffective due to their rapid degradation, low bioavailability, and inefficient targeting to the wound site. The purpose of this review is to discuss the molecular pathophysiology of diabetic wound healing and to assess the potentialof nanotechnology-based drug delivery systems as novel therapeutic approaches for the management of DFUs.</p> Methods <p>A comprehensive literature search was carried out using the PubMed, Scopus, and Web of Science scientific databases. The search was restricted to articles published until 2025. The keywords used for the search were “diabetic wound healing,” “nanoparticles,” and “drug delivery systems” to obtain information on the molecular pathophysiology of diabetic wound healing and the latest developments using nanoparticles. Relevant in vitro, in vivo and, clinical studies involving the application of nanoparticles, hydrogels, and bioengineered scaffolds in the treatment of wounds was considered. This study is presented as a narrative review.</p> Results <p>Delivery systems based on nanotechnology showed substantial benefits over traditional therapies by protecting bioactive molecules from degradation, improving cellular uptake, and achieving controlled and sustained release. Nanoparticles helped improve drug stability and penetration, hydrogels provided a similar ECM with a moist environment around the wound, and bioengineered scaffolds aided tissue regeneration with a controlled release of therapeutic agents. Surface-modified and responsive nanocarriers exhibited improved therapeutic efficacy.</p> Conclusion <p>Nanotechnology provides a promising solution to address the major drawbacks associated with the treatment of DFUs. By integrating molecular abnormalities with precision-based drug delivery, nanomedicine provides novel solutions to expedite wound healing and minimize complications associated with diabetic wounds.</p> Lay Summary <p>DFUs are a serious complication of diabetes, which often results in infection, hospitalization, and amputation due to poor healing of the wound. Poor angiogenesis, chronic inflammation, and tissue repair are some factors that hinder the healing process, and the conventional treatment methods are ineffective due to poor stability and lack of efficient drug delivery. This review focuses on the use of nanotechnology-based drug delivery systems, which are promising alternatives for the treatment of DFUs. Nanomaterials such as nanoparticles, hydrogels, and bioengineered scaffolds can protect drugs from degradation, promote efficient drug delivery, and facilitate tissue regeneration.</p> Graphical Abstract <p>Schematic representation of Nanomaterial-based therapeutic outcomes for addressing the adverse effects of diabetic wounds </p> <p></p>