The prevalence of metabolic syndrome is rising steadily due to increased consumption of high-fat diet. This study evaluates the effects of red, green, and black pepper varieties on the liver enzymes of wistar rats fed with a high-fat diet. The study involved 35 wistar rats separated into seven groups of five rats each. The animals were fed with high-fat diet consisting of butter throughout the period of the experiment. Group 1 is untreated and received only high-fat diet. Groups 2 and 3 received additional 50mg/kg and 75mg/kg of red pepper respectively, Groups 4 and 5 received additional 50mg/kg and 75mg/kg of green pepper respectively, Groups 6 and 7 received in addition 50mg/kg and 75mg/kg of black pepper respectively. The experiment lasted for 28days and thereafter, blood samples were collected to determine the serum concentrations of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). The results showed that of all the pepper types used in our study, only the high dose of black pepper significantly increased all the liver enzymes measured. The AST and ALT concentrations were not altered by administration of red pepper, low dose of black pepper and high dose of green pepper. At both concentrations (50mg/kg and 75mg/kg) the three pepper types respectively increased ALP levels and this is possibly attributable to intestinal stimulation. Conclusively, red, green and low dose black pepper possibly exhibited no deleterious effect on the liver. However, our study suggests that consumption of high dose of black pepper might be hepato-toxic. Further research is needed to elucidate underlying mechanisms and optimize therapeutic strategies.