Abstract <p>The synthesis of benzofuranyl coumarins from 4-(bromomethyl)coumarin and 2-hydroxy-4-methoxybenzophenone in dry acetone and in the presence of anhydrous K₂CO₃ in good yield is reported. Single-crystal X-ray structure determination confirmed the molecular structure of 4-(6-methoxy-3-phenyl­benzofuran-2-yl)-7-methyl-2<i>H</i>-chromen-2-one (<b>4a</b>). Protein denaturation inhibition and membrane stabilization assays were used to evaluate the in vitro anti-inflammatory activity of the synthesized compounds. 4-[(2-Ben­zoyl-5-methoxyphenoxy)methyl]-6-ethyl-2<i>H</i>-chromen-2-one (<b>3b</b>) showed the highest protein denaturation inhibition of 77.83±0.47% at a concentration of 100 μg/mL. 4-[(2-Benzoyl-5-methoxyphenoxy)methyl]-6-(propan-2-yl)-2<i>H</i>-chromen-2-one (<b>3c</b>) showed the strongest hemolysis inhibition by 90.43±0.42%. Molecular docking was performed with proteins involved in the inflammatory pathway. In addition, in silico studies were carried out to assess the ADMET profile of the synthesized benzofuranyl coumarins.</p>