Background: Diabetic neuropathy is defined as the dysfunction of the peripheral nervous system in diabetic patients. It is considered a microvascular complication of diabetes mellitus. Its presence is associated with increased morbidity and mortality. Although several studies have found alterations at somatic motor, sensory levels and at the level of autonomic nervous system in diabetic patients, there is not a systematic approach regarding the differences in neuropathy between the major variants of diabetes, e.g., type 1 and 2 diabetes at both neurological and molecular level. Data sources: we systematically (Medline, Scopus, and Cochrane databases) evaluated the literature related to the difference of neuropathy in type 1 and 2 diabetes, differences in molecular biomarkers. Study characteristics: seventeen articles were selected based on pre-defined eligibility criteria. Conclusions: both superficial sensitivity (primarily thermal sensitivity to cold) and deep sensitivity (such as vibratory sensitivity), have been reported mainly in type 2 diabetes. Cardiac autonomic neuropathy is one of the diabetic complications with the greatest impact at a clinical level but is nevertheless one of the most underdiagnosed. While for type 1 diabetes patients most neuropathy alterations have been reported for the Valsalva maneuver and for the lying-to-standing test, for type 2 diabetes patients, alterations have been reported for deep-breathing test and the Valsalva test. In addition, there is a greater sympathetic than parasympathetic impairment, as indicated by the screening tests for autonomic cardiac neuropathy. Regarding subclinical inflammation markers, patients with type 2 diabetes showed higher blood levels of inflammatory markers such as high-sensitivity C-reactive protein, proinflammatory cytokines IL-6, IL-18, soluble cell adhesion molecules and E-selectin and ICAM-1, than in type 1 diabetes patients. By contrast, the blood levels of adiponectin, an adipocyte-derived protein with multiple paracrine and endocrine activities (anti-inflammatory, insulin-sensitizing and proangiogenic effects) are higher in type 1 than in type 2 diabetic patients. This review provides new insights into the clinical differences in type 1 and 2 diabetes and provide future directions in this research field.