Quercetin is a flavonoid widely found in food and traditional herbs. In this study, we evaluated the anti-aging effects of quercetin on Simocephalus vetulus (S. vetulus) by assessing lifespan and growth parameters and analyzed the differentially expressed proteins and crucial pathways associated with quercetin activity using proteomics. The results demonstrated that, at a concentration of 1 mg/L, quercetin significantly prolonged the average and maximal lifespans of S. vetulus and increased the net reproduction rate slightly. The proteomics-based analysis revealed 156 differently expressed proteins, with 84 being significantly upregulated and 72 significantly downregulated. The protein functions were identified as being associated with glycometabolism, energy metabolism, and sphingolipid metabolism pathways, and the key enzyme activity and related gene expression, such that of AMPK, supported the importance of these pathways in the anti-aging activity of quercetin. In addition, quercetin was found to regulate the anti-aging-related proteins Lamin A and Klotho directly. Our results increased the understanding of quercetin's anti-aging effects.