Anti-aging functional foods have garnered widespread attention for their ability to provide health benefits through daily diets. Picroside I is a natural compound extracted from the rhizome of Picrorhizae Rhizoma. Picrorhizae Rhizoma, a common traditional Chinese medicinal material, is also frequently used as an ingredient in health teas. Its rhizome is rich in various bioactive components. Caenorhabditis elegans, a classic model organism for aging research, holds significant importance in the study of functional foods. In this study, we used C. elegans as a model to investigate the effects of the natural compound Picroside I from traditional Chinese medicine on the lifespan and locomotor ability of the worms. The results showed that Picroside I increased the head thrashing and pharyngeal pumping rates of the worms on day 8, thereby enhancing their muscle vitality. Moreover, Picroside I at a concentration of 10 μM significantly extended the healthspan of the worms. Further network pharmacology and molecular docking analyses revealed that Picroside I may be associated with glycation end-product receptors and lipid metabolism. Additionally, it was found that the compound acts on the disulfide bond region of the asymmetric dimer of kinase domains of the EGFR protein, reducing the stability of the protein and thereby affecting downstream signaling pathways in cells, such as the PI3K/Akt pathway and the MAPK pathway, which in turn influence cellular metabolic processes. Our study indicates that Picroside I has significant potential to extend the lifespan and enhance the muscle vitality of C. elegans. It holds promise as a novel anti-aging food ingredient and is of great significance for the development of traditional Chinese medicine-based anti-aging functional foods.