Elevated body mass index and post-prandial state are associated with disadvantageous choices on the Iowa Gambling Task (IGT). Whether physiological factors including percent body fat, and peripheral glucose, insulin, and leptin concentrations, are associated with IGT performance is unknown. In196 healthy adults without diabetes, we measured body fat by DXA scan, glucose, insulin and leptin (n = 138) concentrations during an oral glucose tolerance test and IGT performance after a standardized meal. Glucose was not associated with IGT performance. Disadvantageous IGT performance was associated with higher percent body fat (r = − 0.16, p = 0.03), 30-min insulin concentrations (insulin30, r = − 0.27, p < 0.001), and 30-min leptin concentrations (leptin30, r = − 0.23, p = 0.008). Mediation analysis demonstrated that leptin30 was almost completely responsible for the percent body fat effect on IGT performance. Even adjusted for age, sex, race, and education, insulin30 (b = − 46.5, p = 0.03) and leptin30 (b = − 50.9, p = 0.03) concentrations remained independently associated with IGT performance and interacted together such that higher leptin30 blunted effects of higher insulin30 (b = 23.8, p = 0.048). These findings may indicate an internal metabolic signature of energy availability (higher body fat, insulin, and leptin levels) associated with disadvantageous IGT performance.