Chronic foot ulcers, especially those that fail to heal, represent a major and escalating global health burden, primarily impacting individuals with diabetes mellitus, peripheral arterial disease (PAD), and other systemic conditions. These non-healing ulcers contribute significantly to morbidity, diminished quality of life, frequent hospitalizations, and, in severe cases, limb loss. The pathogenesis of diabetic foot ulcers is multifactorial, involving ischemia, infection, neuropathy, and impaired wound healing mechanisms. Effective management demands a comprehensive, multidisciplinary approach targeting both local wound conditions and systemic metabolic derangements. Limb preservation, a critical goal in the management of chronic diabetic foot ulcersaims to prevent amputation while promoting wound healing and functional recovery. Therapeutic strategies include offloading pressure from the ulcer site, aggressive infection control, vascular interventions for revascularization, and advanced wound care modalities such as bioengineered skin substitutes, negative pressure wound therapy (NPWT), and topical growth factors. Moreover, stem cell therapy and regenerative medicine approaches are emerging as promising options for enhancing tissue repair and regeneration. This review highlights the complexity of diabetic foot ulcers, emphasizing the systemic and local interplay that hampers healing. It also outlines both established and emerging interventions designed to improve limb salvage and long-term outcomes. A deeper understanding of the molecular and cellular mechanisms underlying chronic wound healing may lead to innovative therapies, ultimately reducing the global burden of diabetic foot ulcers and lowering amputation rates.