Aim: This is a prospective, pilot, open-label, interventional, comparative, randomized study, enrolled 60 patients with type 2 diabetes mellitus (T2DM) to assess the effect of different doses of oral vitamin B containing Benfotiamine 300 mg versus intramuscular B vitamins containing watersoluble Thiamine HCl. Methods Patients ≥ 18 years with T2DM with Peripheral Neuropathy, divided into 3 groups; A & B (Benfotiamine 300 mg) and group C (Thiamine HCl), which were sub-divided to include patients with HbA1c less or more than 8 %. Patients were evaluated at baseline, after 2.5 hours, six days, and two weeks. Results Blood vitamin B1 increased from baseline to after 2.5 hours (T2) by 57%, 79% and 33% in group A, B and C respectively, with statistically significant difference in each group (p value < 0.001). Vitamin B1 continued to increase after six days (T6) in patients of groups A & B by 98% and 165% respectively, while dropped in patients of group C from 33% at T2 to 6% at T6, with p-value ≤ 0.001 between the three groups. Diabetic Neuropathic Symptom Score (DNS) decreased in mean value in all groups after 14 days of treatment by 64.4%, 53.7% and 48.6% in group A, B and C respectively, indicating improvement of peripheral neuropathy. Safety: There was no AE or SAE reported during the study. Conclusion: Oral Benfotiamine 300 mg is safe and more effective than intramuscular Thiamine HCl, in increasing vitamin B1 blood level in patients with diabetic peripheral neuropathy, which in turn relieves peripheral neuropathy. Clinical Trial Registration Number: NA Keywords: Benfotiamine, Bioavailability, Thiamine, Diabetic Peripheral Neuropathy Abbreviations : Adverse Event (AE), Advanced Glycation End products (AGE), Analysis of Variance (ANOVA), Alanine Transaminase (ALT), Body Mass Index (BMI), Case Report Form (CRF), Diabetic Neuropathic Symptom score (DNSS), Diacylglycerol (DAG), Dipeptidyl Peptidase 4 Inhibitor (DPP-4 I), Good Clinical Practice (GCP), Informed Consent Form (ICF), Intent to Treat (ITT), Institutional Review Board (IRB), Ministry of Health (MOH), National Institute of Diabetes and endocrinology (NIDE), Nuclear Factor kappaB (NF-κB), Per Protocol (PP), Protein Kinase C (PKC), Research and health Development (RHD), Serious Adverse Event (SAE), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), Transient Ischemic Stroke (TIA)