At least one in four diabetic patients is affected by peripheral neuropathy. In this study, the MALDI-TOF-MS mass spectra of peptides and proteins were generated following WCX CLINPROT bead fractionation of 39 diabetic peripheral neuropathy (DPN), 39 diabetes mellitus (DM), and 35 control (CON) serum samples. The spectra were analyzed statistically using flexAnalysisTM and Clin-ProtTM bioinformatics software. Identification of the selected markers was performed and affinity bead-purified plasma protein was subjected to LTQ Orbitrap XL MS/MS analysis followed by Mascot identification of the peptide sequences. 89 differentially expressed peaks of serum proteins were identified. 17, 10 and 4 most significant peaks between CON vs. DM, CON vs. DPN, DM vs. DPN, respectively, were selected out using the ClinProTool software package and used to train a Supervised Neural Network. A veracity rate of 100% was obtained for all sets. Following this analysis, a 6631-Da marker was identified as a fragment of the Apolipoprotein C-I precursor. The peptides identified may have clinical utility as surrogate markers for detection and classification of DM and DPN.