Aim The present study aimed to investigate the relationship between advanced glycation end‐product accumulation and skeletal muscle mass among middle‐aged and older Japanese men and women. Methods A total of 132 participants enrolled in this cross‐sectional study. Skin autofluorescence was assessed as a measure of advanced glycation‐end products. Appendicular skeletal muscle mass was measured using dual‐energy X‐ray absorptiometry, and skeletal muscle index was calculated by dividing appendicular skeletal muscle mass by height squared. Participants were divided into two groups (low skeletal muscle index and normal skeletal muscle index) using the Asian Working Group for Sarcopenia's skeletal muscle index criteria for diagnosing sarcopenia. Multivariate logistic regression analysis and the area under the receiver operating characteristic curve were used to determine significant factors associated with low skeletal muscle index. Results Participants consisted of 70 men (mean age 57 ± 10 years) and 62 women (mean age 60 ± 11 years). There were 31 and 101 participants in the low and normal skeletal muscle index groups, respectively. Skin autofluorescence was significantly higher in the low skeletal muscle index group compared with the normal skeletal muscle index group (P < 0.01). Skin autofluorescence was a significant independent factor associated with low skeletal muscle index based on multivariate logistic regression analysis (odds ratio 15.7, 95% confidence interval 1.85–133.01; P = 0.012). The cut‐off for skin autofluorescence was 2.45 arbitrary units, with a sensitivity of 0.75 and specificity of 0.91. Conclusions Skin autofluorescence was an independent factor associated with low skeletal muscle index among middle‐aged and older Japanese men and women. Geriatr Gerontol Int 2017; 17: 785–790.