Resveratrol administered through nasal passages protected brain and retinal tissues from cisplatin-induced damage in rats, though intraperitoneal injection proved more effective. The polyphenol reduced lipid peroxidation, preserved catalase activity, and maintained acetylcholinesterase function while decreasing DNA damage markers like 8-OHdG. Both delivery routes activated anti-inflammatory pathways through IL-10 upregulation and reduced apoptosis via caspase-8 modulation, with enhanced Nrf2 antioxidant signaling. This research addresses a critical clinical challenge since cisplatin's neurotoxic side effects often force treatment discontinuation in cancer patients. The intranasal route offers particular promise for clinical translation, providing a non-invasive alternative to injections while still delivering meaningful neuroprotection. The finding that resveratrol can simultaneously protect both central nervous system and retinal tissues suggests potential for preserving quality of life during chemotherapy. However, the rat model limits immediate human applicability, and optimal dosing remains unclear. While the superior efficacy of intraperitoneal delivery suggests bioavailability challenges with nasal administration, the convenience and patient compliance advantages of intranasal dosing warrant further investigation in human trials.