The bifunctional aldehyde/ethanol dehydrogenase (AdhE) exhibits acetaldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) activities, and is one of the key enzymes in the bacterial ethanol anaerobic fermentation pathway. Researches on bacteria-host interactions revealed that AdhE also plays an important role in bacteria adapting to the internal environment changes and regulating bacterial virulence. In this paper, we summarized the regulatory mechanisms of AdhE on bacterial pathogenesis and host immune, which may provide new perspectives for understanding AdhE’s function.