This study was aimed at investigating the effect of aqueous extract of Mangifera indica leaves on some biochemical parameters and histology of liver, kidney and small intestine of rats. Twenty female rats (142.30 ± 7.56 g) were randomly assigned into four groups A, B, C and D. The rats were administered orally 1 mL of distilled water, 25, 50 and 100 mg/kg body weight of the extract once daily for 10 days. The biochemical parameters were determined using standard methods. All the doses of the extract significantly increased the activities of liver aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and chloride ion (Cl-) content whereas the liver ALT, serum urea, uric acid, potassium ion (K+) and small intestine body weight ratio decreased significantly in a dose dependent manner. The serum concentrations of sodium ion (Na+) and creatinine increased only at 50 and 100 mg/kg body weight of the extract while the levels of total protein, albumin, globulin, conjugated and total bilirubin significantly decreased in the serum. The liver and kidney body weight ratio significantly increased at 100 mg/kg body weight of the extract while the extract at all the doses did not significantly alter the activity of serum AST. Furthermore, the extract significantly decreased the activity of alkaline phosphatase (ALP) in the small intestine of the animals with corresponding increase in the serum. The extract at varying doses produced mild and moderate hepatocellular and submucosa layer degeneration in the liver and small intestine respectively while there was glomeruli shrinkage in the kidney. The extract caused structural and functional toxicity hence, should be consumed with caution.Keywords: Mangifera indica, Anacardiaceae, Structural toxicity, Functional toxicity, Histoarchitectural changes