Matrine is an alkaloid compound isolated and extracted from the traditional Chinese medicinal plant Sophora flavescens, which has anti-tumor, anti-inflammatory, and anti-viral effects. However, its clinical application has been limited due to its low in vivo activity, short duration of efficacy, and significant toxic side effects. In response to this challenge,pharmaceutical experts modified the structure of Matrine to obtain derivatives that addressed its limitations. Currently, research on the anti-tumor effects of Matrine and its derivatives is more prevalent, while research in inflammatory-related diseases still needs further strengthening.The progress on the role and mechanism of Matrine and its derivatives in inflammatory diseases were summarized in this paper, which offered valuable insights for the development of therapeutic agents based on Matrine.