Whenever any plant and/or herb is ingested, the body system interacts with it in an attempt to get rid of any harmful toxins such may contain, especially if the body cannot convert the foreign substance into useful components. This investigation was to evaluate the effects of oral consumption of aqueous leaf extract of Crassocephalum crepidioides on the frontal cortex, kidney, liver and testes of Sprague Dawley rats using microanatomical studies. Twenty adult male Sprague Dawley rats weighing between 165-198 g were used. They were divided into 2 groups. The rats in the treated group A received 300 mg/kg body weight of the aqueous leaf extract of C. crepidioides for thirty days (30d). 6 rats gained increase in body weight. Histopathological observation of their frontal cortex, liver and testes revealed no significant abnormal alterations apart from alterations observed in the kidneys of 4 rats and these include glomerular distortion, vacuolations and evidence of tubular necrotic bodies. The rats in the control group B received equal volume of phosphate buffered saline (PBS) also for 30d. No histopathological abnormalities were seen in the frontal cortex, kidney, liver, and testes of the rats. Aqueous leaf extract of C. crepidioides has histo-toxic effects on the histological profile of the kidneys of the rats. The observed histopathological changes in the kidneys of the treated rats may affect the functional activities of the kidney.