Titanium dioxide (TiO2) is used abundantly as a white pigment with many applications; food coloring agents, additives, tooth whitening paste, pharmaceutical preparations, painting materials, and sunscreen creams. Objectives: The present study aimed to explore the possible toxicological effects of orally administered TiO2. Methodology: Twenty male albino rats were given food-grade TiO2 in a dose of 20 mg/kg BW via oral gavage at 1 mL daily volume for 120 consecutive days. 20 male rats were used as a control group. Liver enzymes (AST, ALT, and ALP), renal function (urea and creatinine), creatine kinase activity (CK-MB isoenzyme), and serum levels of troponin were measured at the end of the study for each rat. Histopathological analysis of cardiac, hepatic, renal, and gastrointestinal tissue sections was also performed for both groups. Results: Increased CK-MB, cardiac Troponin, ALT, ALP, and urea serum levels in TiO2 treated groups were recorded. Histopathological examination showed focal fibrosis of cardiac tissue. Hepatic sections showed inflammation and fat deposits. Gastrointestinal wall inflammations with blunting of the villi all over the small intestine, active inflammation of the colon and kidney tissues in the renal pelvis were found. Conclusion: Prolonged daily oral administration of food-grade TiO2 can induce cardiovascular, hepatic, intestinal, and renal adverse effects.