Onion (Allium cepa L.) is one of the most widely cultivated vegetables worldwide, while its leaves are discarded as agricultural waste despite being a valuable source of bioactive compounds. This study aims to investigate anti-aging cosmetic potential of onion leaf extract obtained by microwave-assisted extraction (MAE). Under optimized conditions (50% ethanol, 50 °C, 15 min, and a 1:20 solid-to-solvent ratio), the total flavonoid content obtained by MAE was approximately 1.34-fold higher than that achieved by conventional maceration. HPLC analysis of the extract identified and quantified quercetin as a major constituent (2.51 ± 0.02 mg/g sample), while LC-QTOF-MS profiling identified 56 bioactive compounds, including flavonoids, phenolic acids, and sulfur-containing groups. The extract showed a total phenolic content of 45.1 ± 1.47 mg GAE/g sample, total flavonoid content of 13.2 ± 2.52 mg QE/g sample, antioxidant activity (DPPH IC₅₀ = 97.1 ± 7.12 µg/mL), anti-glycation activity (IC₅₀ = 213 ± 4.6 µg/mL), tyrosinase inhibitory activity (IC₅₀ = 50.66 ± 2.52 µg/mL), and anti-collagenase activity (IC₅₀ of 2.84 ± 0.03 mg/mL). Cell-based assays using human keratinocytes (HaCat) cells demonstrated that the extract was non-cytotoxic at concentrations up to 100 µg/mL after 24 and 48 h of exposure. Furthermore, cells treated with the extract showed visually lower H₂DCFDA fluorescence following hydrogen peroxide exposure, suggesting a possible reduction in intracellular ROS accumulation. Overall, onion leaves represent a promising natural source of bioactive compounds and could be valorized as a potentially anti-aging cosmetic ingredient.