Cisplatin (CP)-induced neurotoxicity is one of the major clinical problems in CP-based chemoradiotherapy, leading to its discontinuation depending upon their severity. In the present investigation, the photosensitizing property of riboflavin (RF) has been used to ameliorate the CP-induced neurotoxicity. According to dosing plan, the healthy mice were given RF, CP, and their combinations under photoillumination with their controls without any light exposure. After the treatment, antioxidant enzymes, cellular reductants, glutathione-S-transferase, brain markers, and oxidation products were assessed besides histopathology in their brain samples. These parameters revealed that RF ameliorates CP-induced neurotoxicity in a dose-dependent manner under photoillumination. Hence, inclusion of RF in CP-based chemoradiotherapy can be an effective strategy to counter CP-induced neurotoxicity.