Protein-energy wasting (PEW) facilitates major adverse clinical outcomes in chronic renal failure (CRF), with current therapies not suitable for all patients. Faecalibacterium prausnitzii (F. prausnitzii) can alleviate chronic kidney disease, with unclear effects and mechanisms on CRF with PEW. The CRF rat model was constructed by adenine administration, and PEW was induced by a 4% casein diet. The serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) levels were measured by enzyme-linked immunosorbent assay. Pathology of the gastrocnemius muscle was estimated using hematoxylin and eosin staining. The expression of mitophagy-related markers was detected to assess the mitophagy level. Dexamethasone-induced L6 myotubes established myotube atrophy models. The levels of mitophagy-related markers, muscle RING-finger protein-1 (MuRF1), and atrophy gene 1 (Atrogin1) were detected by quantitative reverse transcription-polymerase chain reaction and western blotting. F. prausnitzii suppressed the SCR, UPR, and BUN expression in serum and gastrocnemius muscle atrophy, which were promoted by CRF with PEW. Dexamethasone-induced expression of MuRF1 and Atrogin1 in L6 myotubes was decreased by F. prausnitzii. Additionally, F. prausnitzii repressed mitophagy in the gastrocnemius muscle and L6 myotubes. In conclusion, F. prausnitzii suppressed renal failure progression and muscle atrophy by inhibiting mitophagy in CRF with PEW.