BACKGROUND: Diabetic peripheral neuropathy is one of the most devastating complications of long-term diabetes mellitus, associated with functional limitations and poor quality of life. MATERIALS AND METHODS: Two hundred subjects were randomized into intervention and control group, with one hundred in each arm. The intervention arm received photobiomodulation therapy for ten days, with Low -Level Helium-Neon Laser at a wavelength of 632.8 nm of dosage 3.1 J/cm RESULT: Trial found significant changes in serum NSE (p <
0.001), CGRP(p <
0.001), MNSI(p <
0.001), VPT(p <
0.001), NPRS(p <
0.001), and NQL(p <
0.001) in the intervention group four weeks after receiving photobiomodulation therapy, whereas no changes in NGF levels(p = 0.937). This was in correlation with improved neuropathic pain and quality of life. CONCLUSION: Serum levels of NSE and CGRP may be good indicators of effectiveness of photobiomodulation in reducing neuropathic pain and other symptoms in individuals with DPN. Reduced neuropathic symptoms, improved protective sensation of foot and quality of life, and reduced neuropathic pain was observed in intervention group.