This review highlights the increasing interest in one of the natural compounds called saponins, for their potential therapeutic applications in addressing inflammation which is a key factor in various chronic diseases. It delves into the molecular mechanisms responsible for the anti‐inflammatory effects of these amphiphilic compounds, prevalent in plant‐based foods and marine organisms. Their structures vary with soap‐like properties influencing historical uses in traditional medicine and sparking renewed scientific interest. Recent research focuses on their potential in chronic inflammatory diseases, unveiling molecular actions such as NF‐κB and MAPK pathway regulation and COX/LOX enzyme inhibition. Saponin‐containing sources like Panax ginseng and soybeans suggest novel anti‐inflammatory therapies. The review explores their emerging role in shaping the gut microbiome, influencing composition and activity, and contributing to anti‐inflammatory effects. Specific examples, such as Panax notoginseng and Gynostemma pentaphyllum, illustrate the intricate relationship between saponins, the gut microbiome, and their collective impact on immune regulation and metabolic health. Despite promising findings, the review emphasizes the need for further research to comprehend the mechanisms behind anti‐inflammatory effects and their interactions with the gut microbiome, underscoring the crucial role of a balanced gut microbiome for optimal health and positioning saponins as potential dietary interventions for managing chronic inflammatory conditions.