Diabetes-induced hyperglycemia is a causal factor for cardiovascular disease (CVD) and, specifically, peripheral artery disease (PAD). Metformin is the cornerstone drug therapy for glucose-lowering that exerts beneficial effects beyond glycemic control. New glucose-lowering drugs have recently been shown cardiovascular benefits and their impact on CVD risk is of increasing importance. Current guidelines recommend these novel therapies as second-line options for patients with diabetes and established CVD. Given the prevalence of CVD in this population, a complete understanding of the cardiovascular safety/efficacy of glucose-lowering drugs is needed. The present review provides an update overview of the anti-diabetic drugs and their impact on PAD and cardiovascular outcomes, summarizing key recent trial findings highlights their risk and benefits.