Background <p>Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and severe motor dysfunction. Oxidative stress is recognized as a central cause of its pathogenesis, highlighting antioxidants as promising therapeutic candidates. However, studies that combine the benefits of antioxidants are few.</p> Results <p>Given the prior knowledge of poor bioavailability of curcumin, we combined curcumin with resveratrol to investigate their superior therapeutic potential compared to using each separately in Drosophila melanogaster model of rotenone-induced PD. We evaluated the effects of antioxidant treatment on behavioral, biochemical and cellular parameters associated with neurodegeneration. Findings revealed that when curcumin and resveratrol were combined, the enhancing of climbing performance and modulating key oxidative stress markers, indicating a partial restoration of redox homeostasis, were significantly greater than with treatment with each antioxidant separately.</p> Conclusions <p>This work provides evidence linking curcumin–resveratrol treatment with reduced caspase-mediated apoptosis in a Drosophila model of Parkinson’s disease. Our results provide additional evidence that antioxidant-based strategies may represent a promising avenue for mitigating PD-related neurodegeneration.</p> Graphical Abstract <p></p>