Several studies have suggested a potential effect of serum bilirubin as an antioxidant and cytoprotectant factor. For the results presented here, we evaluated the correlation between serum bilirubin and diabetes mellitus (DM) or chronic kidney disease originated from DM (DMCKD) in a Korean population. We used a cross-sectional, population-based design to examine 93,909 subjects (aged 18-96 years, 53.0% male). The trend of P values in the odds ratios for being DM and DMCKD was calculated using patients separated into five groups based on individual serum bilirubin concentrations. The prevalence of DM and DMCKD was 6.7% and 0.8%, respectively. Higher serum bilirubin levels were significantly associated with decreased prevalence of DM in both men (P trend < 0.001) and women (P trend = 0.014). The risk of DMCKD also decreased as bilirubin levels increased in women (P trend = 0.011), but not in men (P trend = 0.467). Serum bilirubin level was inversely related to insulin resistance using the homeostasis model assessment (HOMA-IR), serum insulin, and C-reactive protein (CRP) levels in multiple linear regression analyses. The regression coefficients (B) of log-HOMA-IR, log-insulin, and log-CRP were as follows: −0.09, −0.13, and −0.60 in men; −0.07, −0.09, and −0.50 in women, respectively. All the regressions were statistically significant (P < 0.001). These results indicate that serum bilirubin might have some protective function against DM and DMCKD, although the association between high serum bilirubin and decreased prevalence of DMCKD is observed only in women.