Pseudorabies virus (PRV) is a member of the genus Varicellovirus in the Herpesviridae family. It primarily causes pseudorabies characterized by reproductive failure in sows, and neurological and respiratory symptoms in piglets, posing a significant threat to pig production. Vaccination is the most important measure to prevent PRV in pigs. However, due to variations of the virus and its latent infection characteristics, the effectiveness of traditional vaccines is compromised. Consequently, there is an urgent need for new drug preparations to assist vaccine immunization. It has been found that natural plant polysaccharides and small molecules such as flavonoids, phenols, and acids can inhibit PRV infection either by directly blocking the viral infection process or by regulating the immune response. In addition, host antiviral protein type Ⅰ interferon and its downstream interferon-stimulated genes have significant inhibitory effects on PRV infection. Host defense peptides, including antimicrobial peptides and defensins, also show good inhibitory effects on PRV infection. Interestingly, researchers have recently found that extracts and metabolites from bacteria and fungi also exhibit anti-PRV effects, and it is expected that these bacteria and fungi and their products could be applied for the prevention and treatment of viral diseases in the future. This study focused on the recent research progress of natural bioactive molecules against PRV infection, aiming to provide important references for the research and development of anti-PRV infection drugs.