BACKGROUND: Plasma 1,5-anhydro-D-glucitol (1,5-AG) may be a easily accessible marker for glycemic variability under mild-to-moderate hyperglycemia. The present study was to investigate the association of 1,5-AG with peripheral nerve function and diabetic peripheral neuropathy (DPN) in patients with T2D and mild-to-moderate hyperglycemia. METHODS: We recruited 574 T2D patients with mild-to-moderate hyperglycemia (HbA1c < 8.0%) for this cross-sectional study, with plasma 1,5-AG synchronously detected. All patients were questioned for neurologic symptoms, examined for neurologic signs and screened for peripheral nerve function. Nerve function included the latency, amplitude and nerve conduction velocity (NCV) of limbs nerves (median, ulnar nerve, common peroneal, superficial peroneal, tibial and sural nerve). Besides, composite Z-score of latency, amplitude and NCV were calculated. DPN was identified as both at least a neurologic symptom/sign and an abnormality of peripheral nerve function. RESULTS: Among the recruited patients, 23.9% (n = 137) were identified to be with DPN, and the prevalence of DPN decreased from 36.6%, 24.5%, 21.2%, 13.3% from first (Q1), second (Q2), and third (Q3) to fourth quartile (Q4) of 1,5-AG. Moreover, multivariable linear regression analysis showed 1,5-AG was associated with composite Z-score of nerve latency (ß = - 0.18, t = - 3.84, p < 0.001), amplitude(ß = 0.26, t = 5.35, p < 0.001) and NCV (ß = 0.24, t = 5.61, p < 0.001), respectively. Furthermore, compared to Q4 of 1,5-AG as reference, the adjusted odds ratios and 95% CIs for DPN of Q3, Q2, and Q1 were 1.29(0.59-2.81), 1.85(0.87-3.97), and 2.72(1.16-6.34), respectively. Additionally, receiver operating characteristic analysis revealed that optimal cutoff value of 1,5-AG to indicate DPN was ≤ 30.8 µmol/L, with sensitivity of 56.20% and specificity of 66.36%. CONCLUSIONS: Low plasma 1,5-AG is closely associated with impaired peripheral nerve function and DPN in T2D patients under mild-to-moderate hyperglycemia.