Background <p>Diosgenin is a steroidal saponin of <i>Dioscorea</i> and <i>Trigonella</i> species, which has been gaining a lot of interest due to its health-promoting action. This review will summarize the potential usefulness of diosgenin, especially with regard to the use of diosgenin in the regulation of gastrointestinal microbiota, the effects, therapeutic mechanisms, utility, and practical implications.</p> Objectives <p>This review aims to comprehensively examine the phytochemistry, extraction techniques, biological mechanisms, and therapeutic potential of diosgenin, with emphasis on its role in gastrointestinal health. A systematic search of peer-reviewed literature published between 2019 and 2025 was conducted via PubMed, Scopus, and Web of Science, prioritizing clinical trials, animal studies, and systematic reviews in accordance with predefined inclusion criteria.</p> Findings <p>Diosgenin has been shown to have the ability to defend the gut, prevent cancer by modifying the signal transduction pathway of NF-kB and MAPK; thereby reinforcing the barrier to the gut and reducing inflammation. Diosgenin is also able to shift the intestinal microbiome in favor of healthy species, including <i>Lactobacillus acidophilus</i> and <i>Bifidobacterium bifidum</i>. Bioavailability may be modulated by new approaches in nanoparticle delivery or macromolecular cyclodextrin complexes.</p> Conclusion and future directions <p>Diosgenin may be applied in the treatment of gastrointestinal-associated conditions such as inflammatory bowel diseases (IBD) and colorectal cancer. What also makes it clinically significant is the capability to achieve the balance of the gut-brain axis. Future clinical trials and pharmacokinetics studies need to be conducted in order to know how diosgenin is demonstrated in functional foods and personalized medicine, and be able to use them in therapies.</p> Graphical Abstract <p></p>