Diabetic retinopathy and diabetic foot ulcer are the most frequent, but also the most disabling complications of diabetes mellitus, with a sinister impact on patients’ quality of life. Microvascular changes related to the deleterious effect of chronic hyperglycemia play an important role in the pathophysiology of both clinical entities by multiple molecular pathways. Vision-threating diabetic retinopathy may be treated by laser photocoagulation, anti-vascular endothelial growth factor (VEGF) agents and vitreoretinal surgery. Diabetic foot lesions are best treated by revascularization if needed, off-loading, infection control and therapeutic adjuncts (e.g. special dressings). Treatment should ideally be offered by a multidisciplinary expert team. Prevention and early detection, along with adequate control of glucose, lipids and arterial hypertension are of paramount importance to avoid and mitigate these fearful complications.