Background and objectivesResearch suggests that diabetic peripheral neuropathy (DPN) is related to high serum uric acid (SUA) level, although its correlation with low SUA level has not been reported. Here, diabetic patients with hyperuricemia were excluded, and the correlation between low SUA level and DPN was explored.Subjects and methodsThis prospective observational clinical study enrolled 525 type 2 diabetes mellitus (T2DM) patients without hyperuricemia, who were divided into the diabetes with symptomatic neuropathy (150 cases), diabetes with asymptomatic neuropathy (125 cases) and diabetes with no neuropathy (250 cases) groups.ResultsThe SUA slightly decreased in subjects with asymptomatic DPN compared with those with no neuropathy and greatly decreased in subjects with symptomatic DPN compared with those without (P< 0.001). The association of the SUA with diabetic neuropathy was independent of the hyperglycemic state and other potential confounders (odds ratio 0.985 [0.981–0.988],P< 0.001). The SUA was closely correlated with the means of motor/sensory nerve amplitude and CV (allP< 0.001). The optimal cut-off point for SUA to distinguish patients with diabetic neuropathy from those without was 324 umol/L, with a sensitivity of 76.0% and a specificity of 79.2% (AUC = 0.806).ConclusionsThe low SUA level is closely associated with DPN. Future studies are warranted to clarify the relationship.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13760-022-01978-1.