Abstract: Diabetic sensorimotor polyneuropathy (DSPN) is the most common complication of type 2 diabetes mellitus (T2DM) and the major cause of nontraumatic lower limb amputation. We aimed in the current research to investigate miR-191-5p as a noninvasive predictive biomarker of DSPN among patients recently diagnosed with T2DM in associations with clinical and electrophysiological tests. Methods: We conducted fifty cases recently diagnosed with T2DM and 50 healthy control subjects. contributors were evaluated by clinical and laboratory investigations in addition to nerve conduction studies. circulatory miR-191-5p assessed using the Real-Time PCR method. Results: miR-191-5p levels were lower in patients with DSPN compared to patients without DSPN and controls. Remarkably, miR-191-5p levels were significantly negatively correlated with cardiometabolic risk factors and neuropathy scores; Neuropathy Disability Score (NDS), Neuropathy Symptom Score (NSS), and Toronto Clinical Scoring System (TCSS), p ˂0.001*. The linear regression test revealed that TCSS, HbA1c, and LDL were the main independent variables against Mir-191-5p levels in patients with DSPN, p ˂0.001*. To assess the predictive values of miR-191-5p we applied the ROC curve the cutoff values of miR-191-5p as a predictive marker for DSPN was (0.559), with a sensitivity of (95%) and a specificity of (98.7%), with the AUC was 0.958 (0.922-0.993), p ˂0.001*). Conclusion: circulating miR-191-5p was significantly downregulated in patients recently diagnosed with T2DM, more specifically in patients with DSPN, and it could be used as a biomarker for predicting diabetes and DSPN.