Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties. In this study, PC12, HepG2 cells, and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms. The results showed that naringin inhibited H2O2-induced decline in cell viability and decreased the content of reactive oxygen species in cells. Meanwhile, naringin prolonged the lifespan of flies, enhanced the abilities of climbing and the resistance to stress, improved the activities of antioxidant enzymes, and decreased malondialdehyde content. Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells. Moreover, naringin down-regulated the mRNA expressions of inr, chico, pi3k, and akt-1, and up-regulated the mRNA expressions of dilp2, dilp3, dilp5, and foxo, thereby activating autophagy-related genes and increasing the number of lysosomes. Furthermore, the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling (IIS) pathway and activating the autophagy pathway, which was consistent with the result of network pharmacological predictions.