Abstract Twenty-three phenolic compounds were isolated from Dioscorea opposita by bioactivity-guided method and their inhibitory effect against pancreatic lipase was evaluated. A total of 15 isolates reduced lipase activity at IC50 values of less than 50 µM and 3,3',5-trihydroxy-2'-methoxybibenzyl showed the highest inhibition with an IC50 value of 8.8 µM. This study is a first to reveal the pancreatic lipase inhibitory activity by both D. opposita and its isolated compounds.