Chronic kidney disease (CKD) is a systemic disorder associated with progressive renal impairment and alterations in metabolism, inflammation, and muscle homeostasis. Muscle wasting represents a major complication of CKD, contributing to physical frailty, poor quality of life, and increased mortality. Accumulating evidence indicates that the kidney–gut–muscle axis plays role in the pathogenesis of CKD-associated sarcopenia. Gut dysbiosis and intestinal barrier dysfunction promote translocation of endotoxins and uremic metabolites into the circulation, amplifying systemic inflammation and muscle catabolism. The present study aimed to investigate whether Phocaeicola plebeius (formerly Bacteroides plebeius), a commensal gut bacterium isolated from healthy human donors, could ameliorate renal injury, restore gut barrier integrity, and improve muscle performance in a murine model of adenine-induced CKD. Male C57BL/6J mice were fed with adenine diet for four weeks to induce CKD and then treated by oral gavage with P. plebeius for eight weeks. Control groups received standard diet. Fecal 16S rRNA sequencing confirmed successful colonization of P. plebeius in the gut of treated mice. Functional assays demonstrated that probiotic administration significantly reduced epithelial permeability, as shown by decreased fluorescein isothiocyanate–dextran (FD-4) flux. In vitro, P. plebeius pretreatment markedly attenuated lipopolysaccharide (LPS)-induced IL-1β secretion from macrophages, suggesting anti-inflammatory activity. Adenine-fed mice exhibited classical features of CKD, including body weight loss, elevated serum creatinine and urea nitrogen levels, microalbuminuria, and severe tubulointerstitial injury with fibrosis. These abnormalities were significantly improved in P. plebeius-treated mice. Moreover, bacteria treatment prevented body weight decline. P. plebeius-treated mice demonstrated a significant increase in latency to fall and improved fatigue resistance compared with the adenine-fed group, reflecting enhanced neuromuscular coordination and muscle strength, via Rotarod test. Overall, P. plebeius confers multi-organ protection in experimental CKD by modulating the kidney–gut–muscle axis, including strengthens intestinal tight junctions, and suppresses systemic inflammatory, which collectively alleviate renal injury and muscle dysfunction. This study provides new evidence supporting the P. plebeius as a next-generation probiotic for CKD management. Future works should be needed to elucidate the molecular pathways for clinical translation.