Abstract Elderly patients with diabetes are at increased risk of frailty and disability in activities of daily living (ADL). Recent evidence has shown that oxidative stress is associated with these conditions. In this cross-sectional study, we aimed to assess whether serum level of bilirubin, a strong endogenous antioxidant, can predict ADL disability in elderly patients with diabetes. Forty elderly patients aged 70 years and older with diabetes and ADL disability and 158 elderly patients with diabetes and without ADL disability were continuously recruited. Multivariate logistic regression models showed that serum bilirubin level was a significant predictor for ADL disability. Receiver operating characteristic analysis showed that the area under the curve (AUC) of serum bilirubin level alone for ADL disability was 0.887 (95% CI 0.837–0.936, P < 0.001) and the cut-off value was 0.4 mg/dL (sensitivity = 88.0% and specificity = 65.0%). The predictive ability was further increased by the addition of age (AUC = 0.921) or addition of age, body mass index, red blood cell count, cerebrovascular disease and chronic renal failure (AUC = 0.953). In conclusion, low serum bilirubin level is a strong predictive biomarker for ADL disability in elderly patients with diabetes, and its clinical utility is suggested.