Abstract: The blood-brain barrier (BBB) constitutes a unique anatomical and physiological interface between the central nervous system (CNS) and the peripheral circulation. It is of critical importance for maintaining the stability of the CNS. This article provides an overview of the changes in the structure of the BBB during the progression of diseases such as aging, neurological disorders, and cancer, with a focus on the effects of gut microbiota and their metabolites on the BBB. Environmental factor-induced changes in the composition of the gut flora disrupt BBB integrity through multiple pathways, whereas gut microbial metabolites have positive, negative, or bidirectional modulatory effects on the BBB. For example, lipopolysaccharide and hydrophobic bile acids have negative effects on the BBB by disrupting cellular structure, decreasing tight junction protein expression, and exacerbating inflammatory responses. The short chain fatty acids, 3-indolepropionic acid, and hydrophilic bile acids have positive effects on the BBB by regulating the intestinal flora, increasing tight junction protein expression, reducing inflammation and exerting antioxidant effects. The trimethylamine oxide has a two-way regulatory effects on the BBB. In addition, different probiotic strains are described to directly or indirectly improve BBB integrity by altering the composition of the intestinal flora, regulating short chain fatty acid levels, enhancing tight junction protein expression, as well as anti-inflammatory and antioxidant pathways. This article provides new strategies and theoretical materials for the treatment and improvement of neurological diseases.