Artesunate-amodiaquine is among the most widely available artemisinin combination therapy used as treatment regimen for uncomplicated Plasmodium falciparum malaria. Our aim was to evaluate clinical routine markers of liver and renal functions, lipid profile levels and lipid peroxidation status in a female mammalian rat model. This was an attempt to simulate a scenario where the drugs are taken without malarial parasite infection, which is a common practice in settings where drug misuse is a common practice. Twenty female Wistar rats were randomly divided into four study groups of five animals each. Group 1 (control) received distilled water, group 2 was exposed to artesunate [2 mg/kg body weight (b.w.)], group 3 was administered with amodiaquine (6.12 mg/kg b.w.) and group 4 was co-administered with artesunate (2 mg/kg b.w.) and amodiaquine (6.12 mg/kg b.w.) for 3 days. At the end of the treatment period, animals were fasted overnight and sacrificed. Markers of liver and renal functions and lipid profile indices were evaluated in the plasma, whereas lipid peroxidation status, GSH concentration and G6PD activity were assessed in the erythrocytes. The results showed that the co-administration of artesunate and amodiaquine altered liver function markers and lipid profile indices. The drugs also induced lipid peroxidation as evidenced by the elevated level of oxidative stress marker malondialdehyde (p < 0.05). We recommend therefore that the drugs should be taken with prescription only with clinical evidence of malarial parasite infection.