Background: Cisplatin (CIS), a widely used chemotherapeutic agent, is known for its severe neurotoxic side effects. This study investigates the neuroprotective effects of gossypin (GOS), a bioflavonoid with antioxidant and anti-inflammatory properties, against CIS-induced neurotoxicity. Methods and results: In-vitro and in-vivo experiments were conducted.50 male Mus Musculus mice were divided into five groups (n:10). Gossypin was administered at varying doses to (in-vitro: 50, 75, 100 µM; in vivo: 5, 10, 20 mg/kg/day) evaluate its protective effects. Results showed gossypin significantly improved cell viability dose-dependently, normalized oxidative stress markers Superoxide dismutase (SOD) activity and glutathione (GSH) and malondialdehyde (MDA) levels, reduced pro-apoptotic and inflammatory genes (CASP-3, CASP-9, TNF-α, NF-kB, iNOS), and increased anti-apoptotic markers (BCL2/BAX ratio, nNOS). Histopathological analysis revealed gossypin mitigated CIS-induced brain tissue damage. Conclusions: Gossypin exhibited significant neuroprotective effects against CIS-induced neurotoxicity via antioxidant (TNF-α), anti-inflammatory (NF-kB), and anti-apoptotic (BCL2/BAX ratio, nNOS) mechanisms by regulating various key regulatory genes, suggesting that it may be a promising adjuvant therapy to protect against the neurotoxic side effects of cisplatin in cancer treatment.