AbstractCarbohydrate‐binding proteins (lectins) are auspicious targets in drug discovery to combat antimicrobial resistance; however, their non‐carbohydrate drug‐like inhibitors are still unavailable. Here, we present a druggable pocket in a β‐propeller lectin BambL from Burkholderia ambifaria as a potential target for allosteric inhibitors. This site was identified employing 19F NMR fragment screening and a computational pocket prediction algorithm SiteMap. The structure–activity relationship study revealed the most promising fragment with a dissociation constant of 0.3±0.1 mM and a ligand efficiency of 0.3 kcal mol−1 HA−1 that affected the orthosteric site. This effect was substantiated by site‐directed mutagenesis in the orthosteric and secondary pockets. Future drug‐discovery campaigns that aim to develop small molecule inhibitors can benefit from allosteric sites in lectins as a new therapeutic approach against antibiotic‐resistant pathogens.