Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus, which reduces the quality of life. However, the association between PDN and environmental factors, especially ambient humidity, remains unclear. Therefore, this study investigated the impact of extreme humidity events on PDN. Data on PDN-related hospital admissions to two tertiary hospitals in Hefei, China (2014-2019) were obtained. A distributed lag non-linear model with a case-crossover design was used to quantitatively estimate the effects of ambient humidity on PDN, and the results were stratified by sex and age. The 1st, 10th, 90th, and 99th percentiles of relative humidity (RHU) were defined as extreme humidity, and the average relative humidity (74.94%) was set as the reference value. Non-linear exposure-response curves between the RHU and PDN cases were obtained. Extreme humidity (92%) had a significant effect on PDN with a relative risk (RR) of 1.13 (95% confidence interval (CI): 1.01-1.26) on a particular day, which increased with the RHU (RR: 1.21, 95% CI: 1.02-1.45 at 98% extreme humidity). Stratification analysis showed that women (RR: 1.38, 95% CI: 1.07-1.77) and patients aged < 65 years (RR: 1.26, 95% CI: 1.01-1.57) were highly susceptible to this effect on the same day. The results suggest that extreme humidity is a crucial trigger for PDN onset in diabetes patients. Furthermore, the effects vary with sex and age. This study provides detailed evidence of the adverse effects of extreme weather on diabetes patients.