Objective: To describe the preparation and characterization of nanoemulsion of sodium salicylate loaded butane tetracarboxylic acid (Bt-Sc-NPs). It also investigates the possible protective effects of Bt-Sc-NPs and\or medicinal plant ginger to evaluate the changes of liver functions, oxidative stress and histopathological investigations against cisplatin-induced hepatotoxicity. Methods: Serum was used to determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), δ-glutamyl transferase (δGT), serum human laminin (LN) and tissue inhibitors of metalloproteinase1 (TIMP1). Liver tissue samples collected from the rats were used for the measurement of malondialdehyde (MDA), nitric oxide (NO) and paraoxonase 1 (PON1). Results: The beneficial effects of Bt-Sc-NPs with its anti-inflammatory effect and the medicinal ginger with its antioxidant effect were observed. Injection of rats with cisplatin significantly increased serum ALT, AST, ɤGT, TIMP1 and LN. It also increased cisplatin-induced oxidative stress by a significant elevation in liver MDA, NO content; however, a significant decrease of PON1 content. While protection with Bt-Sc-NPs or ginger significantly improved these parameters. In addition, combination of both Bt-Sc-NPs and ginger significantly induced a decrease in serum ALT, AST, ɤGT, TIMP1 and LN. It also reduced cisplatin-induced oxidative stress by the significant reduction in liver MDA, NO content and elevation of PON1 content much more than protection with Bt-Sc-NPs or ginger alone. Conclusion: Bt-Sc-NPs were synthesized using nanoemulsion with the help of homogenization and ultra-sonication waves. Combination with both of Bt-Sc-NPs and ginger showed a hepatoprotective role in ameliorating cisplatin‑induced hepatotoxicity due to their anti-inflammatory and antioxidant effects.