Etoposide (ETP) is one of the leading antitumour agents in cancer chemotherapy. Many studies have reported on ETP-induced peripheral neuropathy; however, few reports have focused on its brain toxicity. The current research investigates the protective potential of taurine, piracetam and vinpocetine on serum biomarkers associated with inflammation and brain injury induced by ETP in a rodent model. A total of 30 female albino rats were equally divided into five groups; the 1st and 2nd groups were the control and ETP-treated groups, respectively, while the 3rd, 4th and 5th groups were ETP-treated rats cotreated with taurine, piracetam and vinpocetine, respectively. Administration of ETP reduced body weight significantly, enhanced production of serum proinflammatory cytokines including tumour necrosis factor-alpha, interleukin-1 beta (IL-1β) and IL-6 and decreased glutathione serum levels. Moreover, ETP treatment resulted in upregulation of glial fibrillary acidic protein expression and histopathological alterations in the rats’ brain compared to the control group. Co-treatment with taurine, piracetam and vinpocetine counteracted ETP-induced brain injury and altered serum biomarkers levels. We concluded that co-treatment with vinpocetine could serve as a complementary therapeutic agent in reducing brain injury and toxicity induced by ETP.