Effect of caffeine-coconut products interactions on induction of drug-metabolizing enzyme in Wistar albino rats was studied. Twenty rats were randomly divided into four groups: The control group (1) received via oral route a placebo (4.0 ml of distilled water). Groups 2 to 4 were treated for a 14-day period with 50 mg/kg body weight of caffeine, 50 mg/kg body weight of caffeine and 50 mg/kg body weight of coconut water, and 50 mg/kg body weight of caffeine and 50 mg/kg body weight of coconut milk in 4.0 ml of the vehicle via gastric intubation respectively. One day after the final exposure, the animals were anaesthetized by inhalation of an overdose of chloroform. The blood of each rat was collected by cardiac puncture while the liver of each rat was harvested and processed to examine several biochemical parameters, i.e., total protein and RNA levels, protein/RNA ratios, and activities of alanine and aspartate amino transferase (ALT and AST, respectively). The results showed that while ingestion of coconut milk and coconut water increased the values of protein and protein/RNA ratios, it decreased alanine and aspartate amino transferase (ALT and AST) activities. These effects, in turn, enhanced the induction of the metabolizing enzymes and a resultant faster clearance and elimination of the caffeine from the body, there by reducing the toxic effect on the liver.