Odorant receptors (ORs) in insects are essential for a multitude of behaviors vital to their existence. Nevertheless, we have yet to unravel the identities of the ligands detected by the vast majority of ORs. To remedy this, we present a pioneering workflow based on a structure-based approach that combined docking and electrophysiology. Our method boasts the ability to predict novel ligands for both broadly tuned and specific ORs with great efficacy. This approach reveals unexplored regions within the chemical space detected by these proteins, thus addressing a longstanding gap in conventional experimentations.