Diabetic peripheral neuropathy (DPN) is an extremely common chronic complication of diabetes, and also the one with the most complex and partially understood pathogenesis. In contrast to retinopathy or nephropathy, the risk of neuropathy does not follow closely the degree of glycemic control achieved by patients, and other factors seem to play a larger role in its appearance and progression. Lipid and lipoprotein metabolism is one among such factors. Epidemiological evidence indicates a higher incidence of DPN among patients with diabetes and dyslipidemia, while patients in the active group of clinical trials of statins and fibrates have a reduced incidence. From a biological standpoint, lipid mediators are involved in multiple pathways that lead to nerve cell damage. For these reasons, several interventions that impact lipid metabolism like statins, fibrates, alpha-lipoic acid, gamma-linolenic acid, and coenzyme Q10 (ubiquinone) have been tested as therapies for DPN, with varying results. In this chapter, we summarize the mechanisms by which lipid metabolism relates to DPN, the evidence supporting this hypothesis, and relevant ongoing clinical trials in the field.