Soluble fiber-rich tender cluster bean pod (Cyamopsis tetragonoloba) (CB) and a combination of CB and capsaicin, a thermogenic spice compound, were evaluated for weight-reducing effect in high-fat-fed Wistar rats. Freeze-dried CB and capsaicin were included at 15 and 0.015%, respectively, in the high-fat (30%) diet for 8 weeks. Excretion of dietary fat, fat deposition in adipose, and activities of enzymes involved in lipolysis and lipogenesis were examined. CB and capsaicin additively decreased weight gain in high-fat-fed rats, without affecting feed intake. The antiobesity potential of CB was through impeding fat accumulation in adipose and enhancing fat excretion. Decrease in adipose triglyceride by the combination was higher than their individual effects and was accompanied by enhanced activity of hormone-sensitive lipase-facilitating mobilization of depot fat. Increased fecal excretion of triglycerides by the combination of CB and capsaicin was additive. Whereas the hypolipidemic effect of the combination was higher than their individual effects, the decrease in hepatic cholesterol and triglycerides produced by the combination was additve. Thus, dietary CB significantly checked weight gain and adverse changes in lipid profile in high-fat-fed condition amounting to a cardioprotective effect. These beneficial effects were potentiated by coadministration of capsaicin.