The genus Sedum is recognized for its diverse biological activities; however, the potential anti-depressive properties of Sedum kamtschaticum Fisch. & C. A. Mey. and S. takesimense Nakai, along with their bioactive constituents, remain unexplored. Therefore, this study was conducted to profile the phytochemicals of SK and ST and evaluate their antioxidant, anti-aging, and anti-monoamine oxidase potential in vitro. The 70 % ethanolic extracts of SK and ST showed radical-scavenging, anti-aging, and monoamine oxidase inhibitory activities. Through ultra-performance liquid chromatography-electrospray ionization-high-resolution quadrupole time-of-flight mass spectrometry, three phenolic acids, 12 phenolic glucosides, one ellagic acid, and 14 flavonoids were identified. Notably, four flavonoids were reported for the first time: gossypetin-3,5-di-O-β-d-glucopyranoside-8-O-β-d-xylopyranoside (7), gossypetin-3,5-di-O-β-d-glucopyranoside-8-O-α-l-arabinopyranoside (8), herbacetin-3,5-di-O-β-d-glucopyranoside-8-O-β-d-xylopyranoside (10), and herbacetin-3,5-di-O-β-d-glucopyranoside-8-O-α-l-arabinopyranoside (11), as characterized through mass spectrometry, ultraviolet, electronic circular dichroism, and nuclear magnetic resonance analyses. The biological activity assay revealed that most flavonoids exhibited significant antioxidant and lifespan-extending activities. Moreover, their aglycones-gossypetin and herbacetin-exhibited potent and selective inhibition of monoamine oxidase-B. These findings suggest that gossypetin- and herbacetin-based flavonols, the main active compounds in S. kamtschaticum Fisch. & C. A. Mey. and S. takesimense Nakai, may be employed as lead structures in the development of functional foods or drugs to prevent diseases caused by aging and neurotransmitter imbalances.