Objective: This study aimed to isolate and elucidate the structure of water-soluble constituents from Nelumbo nucifera Gaertn. leaves and evaluate their anti-aging effect. Methods: The natural products were isolated from the 60% aqueous acetone extract of the leaves of N. nucifera by column chromatography on MCI gel CHP 20P, YMC-Gel ODS-AQ-HG, and TSK gel Toyopearl HW-40F. Their structures were elucidated using high-resolution-electrospray ionization-mass spectrometry, one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, and electronic circular dichroism spectroscopy. The anti-aging activity was evaluated in the Caenorhabditis elegans model. Results/Conclusion: One novel flavonoid nuciferanoid (1), together with eleven known compounds, were isolated from the extract of the leaves of N. nucifera. Among them, compound 1 could be a starting point for further development of anti-aging drugs.