The goal of this research was to see if using Cur-NPs could boost curcumin bioavailability and to see whether Cur-NPs could protect rats from Cp-induced hepatotoxicity. Five groups of fifty white albino rats were formed at random. Group I acted as negative control while group II received Cyclophosphamide daily dosage of (5 mg/kg body weight) via oral gavage for 8 weeks. Group III received Cur-NPs at a dosage of (20 mg/kg bw) 3 days a week via oral gavage for 4 weeks. Group IV received CP as group II and treated with Cur-NPs as group III for 4 weeks. Group V received Cur-NPs as protector, for 4 weeks before CP administration as group II with continuous administration with Cur-NPs till the end.At the end of the experiment, blood and tissue samples were obtained for biochemical, antioxidant enzyme, and cytokine level determination. According to the findings, giving CP to rats in group II increased serum liver function enzymes (ALT,AST, and ALP), which was followed by a substantial decrease in serum albumin conc. and tissue antioxidants (GPx, SOD, and CAT) activity, as well as increased levels of cytokines (IL-6, IL-1β). Cur-NPs treatment improved these biochemical changes dramatically, particularly in group V.These findings suggest that Cur-NPs may be a potential hepatoprotective agent for reducing liver oxidative stress caused by various stress factors.