Abstract : Alprazolam (ALP) is one of the most frequently prescribed benzodiazepine group of drugs used in the treatment of anxiety disorders whereas caffeine is frequently consumed in everyday life. In this present work, some clinically important enzymes like aspartate aminotransferase (AST) and alanine aminotransferase (ALT), associated with heart, liver and kidney functions were studied in serum and tissue extracts of Swiss-albino male rat after intraperitoneal administration of them separately and in combination. When the rats (n=6) were treated with ALP or Caffeine separately for two months along with a placebo group (n=6), the levels of both the enzymes increased in serum and tissue extracts. But when both ALP and caffeine were administered together, the increase in enzymatic levels was less than that of their individual treatment. These observations suggest that prolonged usage of ALP or caffeine increase the levels of AST, ALT in serum and tissue extracts due to cellular damage and tissue degeneration, raising a possibility to smash up the general health. While taken together, they cause the cellular necrosis and lower the production of both AST and ALT, causing more destruction to the vital organs.