This study investigated the protective effects of caffeic acid phenethyl ester (CAPE) against rifampicin-isoniazid-induced hepatic and pancreatictoxicity in terms of histopathological deterioration, oxidative stress (paraoxonase-1, total antioxidant status, total oxidant status) and biochemical parameters changes. The side effects of isoniazid and rifampicin treatment on hepatic and pancreatic tissues may be prevented with CAPE.