The β‐clamp is the processivity‐promoting factor for most of the enzymes in prokaryotic DNA replication; hence, it is a crucial drug target. In the present study, we investigated the β‐clamp from Helicobacter pylori, aiming to seek potential drug molecules against this gastric‐cancer‐causing bacterium. An in silico screening of Food and Drug Administration (FDA) approved drugs against the H. pylori β‐clamp, followed by its in vitro inhibition using a surface competition approach, yielded the drug diflunisal as a positive initial hit. Diflunisal inhibits the growth of H. pylori in the micromolar range. We determined the structure of diflunisal in complex with the β‐clamp to show that the drug binds at subsite I, which is a protein–protein interaction site. Successful identification of FDA‐approved molecules against H. pylori may lead to better and faster drug development.