The Difoprev system constituted by a sock loaded with nanocapsules containing a hydrating agent in the diabetic foot is tested. A total of 30 neuropathic outpatients with foot anhydrosis were randomized into group A, treated with the application of the sock with the nanocapsules, and group B wearing only the socks without the nanocapsules. Patients were blindly evaluated with a clinical score, hygrometry, transepidermal water loss, skin temperature, and skin hardness at baseline and after 6 weeks. No difference between the groups emerged at baseline. Although group B showed no changes at the end of the treatment, group A significantly ( P < .05) improved in all the parameters evaluated. No adverse events were recorded in both groups during the study. The use of hydrating agents carried by nanocapsules-loaded socks is safe and effective for the neuropathic diabetic foot.