Increasing entrance of aluminum chloride (AlCl 3 ) in many fields exposes human beings to its biotoxicity. Thereby, the present study assesses the potential ameliorative role of curcumin phytosome (CP) on AlCl 3 -induced hepatotoxicity. Rats were divided into four groups ( n  = 6): group 1 served as control; group 2 received CP (200 mg CP/kg b.wt) for 21 days; group 3 injected three doses of AlCl 3 (30 mg/kg/body weight) every 5 days intraperitoneally; group 4 received CP for 7 days prior to AlCl 3 and then received CP concurrently with AlCl 3 for another 14 days. AlCl 3 markedly increased ( P  < 0.05) the concentrations of AST, ALT, ALP, LDH, total bilirubin, and LPO as well as depleted ( P  < 0.05) albumin, GSH, SOD, and GPx stores in comparison to the control group. These biochemical alterations supported by the lesion observed in histological sections, increasing the expression of caspase-3 and decreasing the expression of Bcl-2. Treatment with CP modulates the hepatic dysfunction, boosting the endogenous antioxidant status, downregulating the expression of caspase-3, and upregulating the expression of Bcl-2. This hepatic ameliorative effect may be mediated by the ability of CP to repair the oxidant/antioxidant equilibrium rather than its ability to suppress apoptosis.