Background <p>Wounds are skin-based or deep-seated, affecting humans by and large. Burn and diabetic wounds are the most common in recent times. Diabetic cutaneous ulcers and diabetic foot ulcers (DFU) are the two significant complications of diabetes that have debilitating effects on patients. Among these, diabetic foot ulcers are the most common, and in patients with DFUs, wounds are complicated to heal, which leads to bacterial and fungal infections. Prolonged and poorly managed diseases often lead to the amputation of legs/and or feet, thereby causing a permanent disability with poor quality of life to the patient. Likewise, burn wounds are often a result of accidents or exposure to heat and include various degrees depending on the severity of the wound. Currently, mesenchymal stem cells and MSC-derived bioactive molecules are considered emerging therapies for enhancing burn and diabetic wound management due to their potential for tissue repair and differentiation.</p> Methods <p>In this review article, a comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus, with the help of keywords: “Burn Wounds,” Diabetic Wounds,” “Mesenchymal Stem Cells, and “Biomaterials.” Inclusion criteria: original, research article, review article, study involving MSCs and biomaterials and scaffolds, in vitro and in vivo study focusing on burn and diabetic wounds, quantitative data related to wound healing. Exclusion criteria: Meta-analysis, conference, and abstracts. Time frame: The systematic literature search was conducted covering the period from December 15, 2000, to May 30, 2025.</p> Results <p>This review explores burn and diabetic wounds and the related complications. Furthermore, the currently available treatments for burn and diabetic wounds have also been discussed. Additionally, potential applications of mesenchymal stem cells and MSC-derived bioactive molecules, as well as nature-inspired biomaterials, were comprehensively reviewed. Furthermore, we explored the molecular mechanisms by which MSCs regulate the critical phases of wound healing.</p> Conclusion <p>This review has covered the immunomodulatory and non-immunogenic properties exhibited by MSCs upon cell transplantation. Finally, the potential wound-healing abilities of available MSC sources and perspectives on combinatorial approaches using MSCs with biomaterials and drugs have also been evaluated. Moreover, the use of MSCs and their bioactive molecule, along with biomaterials, offers a transformative approach for burn and diabetic wound management.</p> Lay summary <p>Burn and diabetic wounds are a significant global health issue. While current treatments show some effectiveness, they have not yet achieved complete healing. This review focuses on stem cell-based therapy, especially mesenchymal stem cells, due to their strong tissue repair capabilities and ability to modulate the immune system. The use of MSC-derived bioactive molecules is also discussed. Additionally, we briefly review how biomaterials can improve the transplantation of mesenchymal stem cells (MSCs) and MSC-derived bioactive molecules to targeted areas. MSCs and their bioactive molecules could provide a promising approach for treating burn injuries and diabetic wounds in the future.</p> <p>However, additional research is necessary to enhance the effective delivery, cytocompatibility, and stability of MSCs and MSC-derived products to realize better outcomes. We are confident that continued investigation will facilitate clinical translation from laboratory to patient care soon, potentially helping to address this worldwide health issue.</p> Graphical Abstract <p>Role of MSCs in the treatment of burn and diabetic wounds</p> <p></p>