The gut-brain axis has been a subject of significant interest in recent years. Understanding the link between the gut and brain axis is crucial for the treatment of disorders. Here, the intricate components and unique relationship between gut microbiota-derived metabolites and the brain are explained in detail. Additionally, the association between gut microbiota-derived metabolites and the integrity of the blood-brain barrier and brain health is emphasized. Meanwhile, gut microbiota-derived metabolites with their recent applications, challenges and opportunities their pathways on different disease treatment are focus discussed. The prospective strategy of gut microbiota-derived metabolites potential applies to the brain disease treatments, such as Parkinson's disease and Alzheimer's disease, is proposed. This review provides a broad perspective on gut microbiota-derived metabolites characteristics facilitate understand the connection between gut and brain and pave the way for the development of a new medication delivery system for gut microbiota-derived metabolites.