Inspired by the similar antioxidant effect functions of Glabridin and Totarol, we investigates their synergistic anti-aging effects and the underlying metabolic intervention in Caenorhabditis elegans (C. elegans). Various concentrations of Glabridin and Totarol, individually and in combination, were administered to C. elegans, and their impacts on lifespan, body development, motility, oxidative stress resistance, reactive oxygen species (ROS) levels, lipofuscin accumulation, antioxidant enzyme levels, and gene expression were evaluated. The combined treatment significantly extended the lifespan by 37.3% and showed enhanced effects over individual treatments on C. elegans. Metabolomic profiling using LC-MS revealed that the combination modulated aging-related metabolic pathways, particularly those involving NAD⁺/NADH balance and insulin signaling. The synergistic action elevated antioxidant enzyme activities, reduced ROS levels, improved oxidative stress tolerance, and upregulated key genes like daf-16. These findings suggest that the combined administration of Glabridin and Totarol exerts profound anti-aging effects through synergistic interactions, enhancing metabolic regulation and stress resistance. This study provides new insights into their mechanisms of action and highlights their potential as a novel strategy for developing products for anti-aging.