Andrographolide, a diterpenoid component found in traditional Chinese medicine Andrographis paniculata, is known as a natural antibiotic and can be used to treat inflammatory lesions of various systemic diseases. In recent years, andrographolide derivatives have been continuously synthesized and have shown good anti-inflammatory pharmacological activity. These derivatives are mainly obtained by chemical synthesis methods, for example, by altering the hydroxyl and double bond groups in the molecule of andrographolide and introducing different substituents, thus obtaining derivatives with different biological activities and pharmacological properties. This paper summarizes the anti-inflammatory mechanism of andrographolide derivatives and the progress of pharmacological research in inflammatory diseases, such as viral infectious diseases, respiratory or lung injury, gastrointestinal diseases, liver injury, and neurological disorders. It also incorporates the results of our own team's research to deeply explore their therapeutic potential in different inflammatory diseases, which provides direction and rationale for in-depth follow-up research.