A hybrid compound combining deferiprone with resveratrol successfully restored mitochondrial protein expression in β-thalassemia mice suffering from hepatic iron overload. Proteomic analysis revealed that iron accumulation severely downregulated key mitochondrial proteins, particularly frataxin and oxidative phosphorylation components, while DFP-RVT treatment reversed this damage pattern. This mechanistic insight extends beyond β-thalassemia to broader aging research, where mitochondrial dysfunction and iron accumulation represent fundamental drivers of cellular deterioration. The liver findings are particularly relevant since hepatic mitochondria decline significantly with age, and iron dysregulation contributes to age-related diseases including neurodegeneration and cardiovascular disease. While this mouse study demonstrates proof-of-concept for mitochondrial rescue through targeted iron chelation, translation to healthy aging applications remains speculative. The hybrid approach of combining an established iron chelator with resveratrol's antioxidant properties represents innovative pharmacological design. However, the therapeutic window between beneficial iron reduction and essential iron depletion requires careful investigation in human studies before considering applications beyond iron overload disorders.