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INTRODUCTION Curcumin is a naturally occurring compound that has antioxidant properties, acts as a hepatoprotective, and lowers lipid peroxidation. However, curcumin's low solubility and bioavailability are its primary drawbacks and prevent its use as a therapeutic agent. In this study, curcumin nanoparticles will be created using the ultrasonic-assisted extraction method, and their effectiveness against paracetamol-induced changes in ALT, AST, SOD, MDA, and TNF-α will be compared to that of pure curcumin. PURPOSE This study aimed to determine the hepatoprotective effect of curcumin nanoparticles in paracetamol-induced rats as a model for liver injury. METHODS Thirty-six male Wistar rats, aged 6 to 8 weeks, with a minimum weight of 120 grams, were used in an experimental laboratory investigation with a post-test-only group design. Rats in each group received 100 mg/kgBW pure curcumin, 100 mg/kgBW curcumin nanoparticles, and 50 mg/kgBW curcumin nanoparticles for 7 days before paracetamol induction. On day 8, 300 mg/kgBW of paracetamol was intraperitoneally injected to cause liver damage. One of the groups received NAC as an antidote 10 hours after paracetamol induction. Detection of ALT and AST using a Chemistry Analyzer. ELISA approach for the detection of SOD, MDA, and TNF-α. The Roenigk score was calculated by two examiners after the liver histopathology preparations were stained using the Hematoxylin-Eosin method. Post hoc analyses were performed after the One Way Annova and Kruskal Wallis tests to examine the data. RESULTS According to PSA results, the smallest formula that formed curcumin nanoparticles (10.2 nm) was 8 g of curcumin formula mixed with a mixture of Tween 20 4.5 ml, Kolliphor EL 1.5 ml, Propylene Glycol 1.5 ml, and Capryol 90 1 ml for 21 minutes using an ultrasonic process. MDA and TNF-α levels, as well as the liver's histological Roenigk score, were significantly lower in the 100 mg/kgBB pure curcumin group (C100) when compared to the model group (model). The levels of AST, MDA, TNF-α, and the liver histopathology score were significantly lower in the 100 mg/kgBB (NC100) and 50 mg/kgBB (NC50) curcumin nanoparticle groups compared to the model group (model) and pure curcumin group (C100) (p< 0.05). CONCLUSION Curcumin nanoparticles showed better hepatoprotective ability than pure curcumin.