Chronic kidney disease (CKD) is a growing global health burden, affecting millions and contributing to significant morbidity and mortality. Gut microbiome dysbiosis disrupts the gut-kidney axis, reducing beneficial short-chain fatty acids (SCFAs) like butyrate and propionate. SCFAs play a crucial role in mitigating CKD progression through immune modulation, reducing systemic inflammation, and enhancing gut barrier integrity. Emerging therapies targeting the gut microbiome, including prebiotics, probiotics, and fecal microbiota transplantation, show promise in restoring microbial balance and enhancing SCFA production. These interventions demonstrate potential in reducing uremic toxins, improving renal outcomes, and slowing CKD progression. However, challenges remain, including the variability in microbiome profiles, limited large-scale clinical trials, and regulatory barriers. Personalized approaches and robust multicenter trials are essential to optimize these therapies and establish their long-term efficacy and safety. This review explores the interplay between gut microbiome dysbiosis, and SCFAs in CKD. It highlights the therapeutic potential of microbiome-based interventions and emphasizes the need for further research to address existing limitations, paving the way for innovative strategies in CKD management