Diabetes mellitus (DM) represents a major risk factor for all types of cardiovascular disease, including peripheral artery disease (PAD). Cardiovascular events are the most important cause of mortality in patients with diabetes mellitus. About one-third of patients with PAD have also diabetes. The prevalence of PAD can be underestimated in patients with DM, because they are often asymptomatic until they progress to advanced disease and because of the simultaneous diabetic neuropathy. In patients with diabetes, the distal arteries, below the knee, such as popliteal, anterior or posterior tibial, peroneal arteries, are usually affected. Typical claudication is less frequent in patients with DM, so many diabetic patients are asymptomatic a long time, they are diagnosed in more advanced stages and have a worse prognosis. The control of glucose blood level to maintain HbA1c less than 7% is necessary in patients with DM and PAD to reduce the complications. The main treatment in type 2 DM is represented by oral antidiabetic drugs, so 56.9% of the patients with type 2 diabetes receive oral antidiabetic agents. Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) can decrease the rate of cardiovascular events, including mortality, in patients with DM and cardiovascular disease. At the moment, SGLT2-i are the most effective and promising oral antidiabetic drugs for patients with DM and PAD. Glucagon-like peptide-1 receptor agonist (GLP-1), liraglutide and semaglutide, also reduce the rate of cardiovascular events. Dipeptidyl peptidase-4 inhibitors (DPP-4) have pleiotropic effects, such as improving endothelial dysfunction, reducing blood pressure and inflammation and may have a protective effect against cardiovascular disease, to delay the progress of atherosclerosis and decrease the risk of PAD. DPP-4 are particularly useful in association with metformin. Thiazolidinediones have an important effect in preventing cardiovascular disease by improving insulin sensitivity in peripheral tissues. Pioglitazone may reduce atherosclerosis by improving insulin resistance and decreasing systemic inflammation which are involved in atherosclerotic plaque formation. Pioglitazones reduce the risk of developing cardiovascular events - myocardial infarction, stroke, compared to placebo in patients with clinically manifest vascular disease. In conclusion, good control of glucose blood levels in patients with DM can reduce significantly the risk of developing PAD.