The C-peptide is a by-product of proinsulin cleavage with recently identified probable pleiotropic protective effects in type I diabetic peripheral neuropathy (DPN). Up to now, through its physiological mechanisms like activating nitric oxide synthase, Na+/K+-ATPase and inhibiting NF-Pathway, C-peptide can not only improve nerve blood flow and alleviate axonal injury, but also have antioxidant and anti-apoptotic effects. Apart from the molecular mechanism level, animal experiments showed that C-peptide could significantly improve nerve conduction velocity, blood flow and structural abnormalities in diabetic rats. Clinical trials have also shown that C-peptide replacement therapy improves nerve conduction velocity and vibration sensation in patients, and the long-acting formulation Peg-C peptide has more promise. Therefore, C-peptide may have a potential protective effect and clinical application prospect in type I DPN. Although it has been proven that C-peptide has an effective role in improving neurological function, its mechanism in the treatment of neuropathic pain has not yet been specifically elucidated. Furthermore, its effect on neuropathic pain symptoms, optimal dosing regimen, and effect on intraepidermal nerve fiber density (IENFD) still need further study.