<p>Advanced glycation end products (AGEs) are associated with osteoporosis (OP) in the diabetic population. However, their relationship with OP in the non-diabetic population remains unclear. This study aimed to investigate cross-sectional associations of AGEs levels in the skin and lens with OP in the non-diabetic population. A retrospective analysis of clinical data of 652 participants was conducted. Bone mineral density (BMD) was quantified by dual-energy X-ray absorptiometry. Lens and skin AGEs were assessed by lens and skin autofluorescence (LAF and SAF). This study included 652 individuals, 280 males (42.9%) and 372 females (57.1%), with a mean age of (55.5 ± 6.9) years. The population with osteopenia exhibited significantly higher levels of SAF–AGEs than those with normal BMD, while the population with OP had significantly higher levels of both SAF– and LAF–AGEs. After adjusting for age and body mass index, LAF–AGEs were negatively correlated with BMD at the femoral neck and total hip. In contrast, SAF–AGEs were negatively correlated with BMD at the lumbar1–4 spine. Furthermore, multiple linear stepwise regression analysis demonstrated that LAF–AGEs were negatively associated with BMD at both the femoral neck and total hip. However, SAF–AGEs showed no association with BMD at any of the three measured sites. Additionally, after adjusting for other covariates, the logistic regression analysis emphasized that LAF–AGEs were associated with OP in the non-diabetic population, but SAF–AGEs do not. The results revealed a significant correlation between LAF–AGEs and OP in the non-diabetic population and their potential clinical utility warrants further validation. Therefore, we urge for larger longitudinal analyses and experimental research to validate and extend these cross-sectional findings.</p>