<p>A new sulfonyl flavonol glucoside, 5,7,4′,5′-tetrahydoxyflavonol 2′-[propanoic acid-(2″′-acetoxy-1″′-sulfonyl)]-5′-O-β-d-glucopyranoside (<b>1</b>) was isolated from the aerial parts of <i>Cotula anthemoides</i> L. in addition to 15 known compounds (<b>2</b>–<b>16</b>). 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 <b>6</b> showed a high DPPH radical scavenging with EC<sub>50</sub> value of 9.1 ± 0.4 μM. Compound <b>11</b>, <b>9</b> and <b>1</b> exhibited a mild tyrosinase inhibitory activity with IC<sub>50</sub> values of 85 ± 0.8, 95 ± 1.5 and 100 ± 0.5 μM, respectively.</p