Objectives: To evaluate the adverse effects of amoxicillin and doxycycline On liver and kidney functions of rats. Material and methods: Twenty-seven male wister albino rats were used and divided randomly into 3 groups’ each of 9 rats. Group (1): were served as control and administered 0.5 ml saline orally for 5 consecutive days. Group (2): were served as amoxicillin group and administered 50 mg/kg amoxicillin trihydrate orally for 5 consecutive days. Group (3): were served as doxycycline group and administered 18 mg/kg body weight doxycycline hyclate orally for 5 consecutive days. Results: Amoxicillin induced significant increases in serum AST, ALT, direct bilirubin, total protein, creatinine and urea levels. Serum of doxycycline treated rats showed significant increases in serum AST, ALT, total protein and urea levels. Histopathological investigations were further supported the biochemical data of adverse effects on liver and kidney. On conclusion; amoxicillin or doxycycline induced significant damage in liver and kidney, therefore dose should be adjusted especially with patients who suffered from history with liver or renal impairment. Hepatic and renal function tests should be monitored before drug prescription especially for long period. Also, dose and duration of therapy should be adjusted.