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To assess the effect of methanolic leaf extract of Caladium bicolor on the histomorphology of gastrointestinal tissues of experimental animals. Twenty four Wistar rats (weighing between 175-190 g) were randomly and equally divided into four groups which include one control group (CG) and three treatment groups (TG I, TG II and TG III). The CG was administered with distilled water [2 ml/kg body weight (b.w.)] while TGs I, II and III were administered with 100 ml/kg, 200 ml/kg and 300 ml/kg (b.w.) of C. bicolor extract respectively. All administrations were done orally and once daily for a period of thirty days. The body weight of all animals was recorded at the beginning and end of study. After the period of study, gastric and small intestinal tissues of experimental animals were harvested, processed, converted to tissue blocks and sectioned. Tissue sections were stained using Haematoxylin and Eosin (H&E) technique. Thereafter, stained sections microscopically examined for observable histopathological changes within study tissues. The results of this study showed that exposure to C. bicolor extract causes significant (p < 0.05) body weight loss in TGs I-III compared to CG. In addition, prominent histopathological changes were observed in gastrointestinal tissues of experimental animals in TGs I-III including gastric mucosal surface erosion and intestinal villi degeneration compared to normal gastrointestinal histomorphology of CG animals. These histopathological changes may be associated with toxic effect of phytochemicals constituents of the extract. Therefore, its application for therapeutic purposes needs to be thoroughly re-validated or perhaps disallowed where alternative therapeutic agents with minimal toxic potential exist.