Mesenchymal stem cells (MSCs) have shown great promise in the treatment of diabetic foot ulcers due to their multipotent differentiation potential, self-renewal capacity, and biological characteristics such as pro-angiogenesis, immunomodulation, and anti-inflammation. Numerous clinical studies and systematic reviews have demonstrated that MSC transplantation is generally safe, with a low incidence of serious adverse events and mild, reversible major side effects. MSCs can exert therapeutic effects by improving local ischemia, promoting angiogenesis, and accelerating wound healing. Some randomized controlled trials and meta-analyses have shown that they are superior to conventional treatments in terms of ulcer healing rate, limb perfusion indicators, and quality of life improvement. MSCs from different tissue sources each have their own advantages in terms of proliferation capacity, immunomodulatory effects, and clinical efficacy. However, the clinical translation of MSCs still faces challenges such as variations in cell quality, lack of standardization in preparation procedures, limitations in large-scale production, and unclear long-term safety and efficacy. Larger sample sizes and more rigorously designed clinical studies are still needed to further clarify the efficacy evaluation system and optimal application strategies, and promote the standardized and sustainable clinical application of MSCs in diabetic foot ulcers.