A new sulfonyl flavonol glucoside, 5,7,4′,5′-tetrahydoxyflavonol 2′-[propanoic acid-(2″′-acetoxy-1″′-sulfonyl)]-5′-O-β-d-glucopyranoside (1) was isolated from the aerial parts of Cotula anthemoides L. in addition to 15 known compounds (2–16). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D-, 2D-NMR and HR-ESI-MS techniques and by comparing their NMR data with those reported in the literature. These compounds were evaluated for their DPPH radical scavenging and tyrosinase inhibitory activity. Compound 6 showed a high DPPH radical scavenging with EC50 value of 9.1 ± 0.4 μM. Compound 11, 9 and 1 exhibited a mild tyrosinase inhibitory activity with IC50 values of 85 ± 0.8, 95 ± 1.5 and 100 ± 0.5 μM, respectively.