Objective: The present study was undertaken to evaluate the possible ameliorative role of curcumin, capsaicin and their combination against lipopolysaccharide (LPS) induced hepatic toxicity in mice. Methods: Animals were distributed into five experimental groups: Normal control, vehicle control, curcumin, capsaicin and combined curcumin and capsaicin treatment groups respectively, for 7 days prior to LPS induced liver toxicity (3 mg/kg b.w. in saline). Hepatoprotective effect of individual and combined spice principles were evidenced by the measurement of serum marker enzyme activities such as, SGPT, ALP and TB and it was further confirmed by histopathological observation of liver tissue section. Results: The administration of LPS increased serum nonspecific enzymes (SGOT; 174.2±3.79 IU/L, SGPT; 124.0±3.14 IU/L, ALP; 320.15±3.88 IU/L and total bilirubin level; 2.32±1.23 mg/dL), however dietary curcumin and capsaicin decreased the activities of these non–specific serum enzymes including total bilirubin indicating amelioration of the severe LPS induced hepatotoxicity, while the combined spice principles were more significant as shown by the levels of enzymes activities SGOT; 89.9±1.39 IU/L, SGPT; 85.9±1.83 IU/L, ALP; 138.4±2.05 IU/L including total bilirubin level; 0.86±0.03 mg/dL. Conclusion: Dietary curcumin and capsaicin individually are protective to LPS induced hepatotoxicity, the beneficial effect was found to be more when the two compounds were fed in combination.