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The aim of the present study was to determine the effect of CD upon biochemical, histological and metabolic alterations induced by drugs that affect hepatic functional integrity and various drug metabolizing systems via distinct mechanisms. For this purpose, paracetamol (ACET) or phenobarbital (PB) were administered to male Wistar rats that were fed with standard rodent chow (normally fed, NF) or underwent dietary CD. The administration of ACET increased the serum aspartate aminotransferase levels in NF rats, while CD restricted this increase. On the other hand, ACET suppressed alkaline phosphatase levels only in CD rats. Moreover, CD prevented the PB\u2010induced increase of the mitotic activity of hepatocytes. The administration of ACET down\u2010regulated CYP1A2 and CYP2B1 expression in CD rats, while up\u2010regulating them in NF rats. The administration of PB suppressed CYP1A2 apoprotein levels in CD rats, whereas the drug had no effect on NF rats. The PB\u2010induced up\u2010regulation of CYP2B, CYP2E1 and CYP1A1 isozymes was markedly higher in CD than in NF rats. In addition, PB increased glutathione\u2010<jats:italic>S<\/jats:italic>\u2010transferase activity only in CD rats. Hepatic glutathione content (GSH) was suppressed by ACET in NF rats, whereas the drug increased GSH in CD rats. Our data suggest that CD has a significant impact on the hepatic metabolic functions, and in particular on those related to drug metabolism. Thus, CD may modify drug effectiveness and toxicity, as well as drug\u2013drug interactions, particularly those related to ACET and PB. 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