Salicylates are the group of chemicals that has salicylic acid as the parent compound and have the ability to treat inflammation, pain syndromes, brain and cardiovascular disorders. The present study was designed to investigate the protective effect of loaded sodium salicylates on nanoparticles to treat brain toxicity induced by cisplatin and decrease the drug side effects. Cisplatin 20 mg/kg BW was given alone or in combination with sodium salicylate loaded on nanoparticles (Si-Sc-NPs) [100 mg/kg BW] for three weeks. The obtained results indicate that Si-Sc-NPs decrease oxidative stress markers such as malondialdehyde (MDA), nitric oxide (NO), and paraoxonase-1 (PON-1) activity in brain. There were also decreased in Monocyte Chemo-attractant Protein-1 (MCP-1) activities and Nuclear Factor kappa β (NF-kβ) level of brain tissue while the Butyrylcholinesterase (BChE) activities of brain tissue increased after Si-Sc-NPs treatment. Histopathological results showed that cisplatin group showed several neurodegenerative changes, on the other hand, group treated with Si-Sc-NPs +Cis showed improvement in almost brain structure and mild pyknotic nuclei and apoptotic neurons were observed.