Artemisinin-based combination therapy had been recommended for the treatment of uncomplicated malaria in Africa.       Aim: This study investigated the effects of artesunate/amodiaquine (A/A) and dihydroartemisinin/ piperaquine (D/P) on some blood parameters and histopathology of the liver and kidney of mice. Materials and Methods: A Complete randomized design was applied. Fifty mice were randomly assigned to five treatment groups of ten animals each. Therapeutic doses of the drugs were orally administered to the animals. Group A received normal saline (control), group B received 10/14mg/kg body weight of artesunate/amodiaquine for 3 days, group C received 10/18mg/kg of dihydroartemisinin/piperaquine for 3 days, group D received similar treatment with group B, but were followed up to 28 days, group E received similar treatment with group C but were also followed up to 28 days. After experimental period, blood samples were collected for determination   of white blood cell count, white blood cell differential count, red blood cell count, packed cell volume and haemoglobin concentration. Liver and kidney were also harvested for histopathological analysis. Results: Result showed that therapeutic doses of artesunate/amodiaquine and dihydroaretmisinin/ piperaquine had no significant (P>0.05) effects on heamatological parameters accessed. Mild inflammation and degeneration of hepatocyte were observed in the liver of the group treated with D/P while fatty change was found in the group treated with A/A.  Venous congestion was observed in the kidney of the group treated with D/P. After 28 days, degeneration of hepatocyte and inflammatory cells were observed in the liver. Shrunken glomerulus was found in the kidney of the group treated with D/P. Conclusion: These drugs are detrimental to the liver and kidney even at therapeutic dose therefore, they should be used with caution.