After a brief presentation of both the pathophysiology of DF and the pharmacology of this promising anti-diabetic oral agent, we will subsequently discuss the effect of SGLT2-i on the multifaceted components of diabetic foot, such as the immunomodulatory effect on the vascular system, neuropathy, peripheral artery disease, risk of infection, and risk of amputation. Here, SLC5A2 is linked to neuropathy.