Cancer cachexia, a debilitating syndrome characterized by muscle wasting and systemic inflammation, remains a major unmet clinical need. Qingxie Fuzheng Granules (QFG), a traditional Chinese medicine formulation, have shown promise in cancer therapy, but their role in cachexia management is unclear.Here, we investigated the anti-cachectic effects of QFG in a murine model of colon adenocarcinoma-induced cachexia. 16S rRNA sequencing revealed gut dysbiosis in cachectic mice, with increased Enterobacteriaceae and decreased Lactobacillus. QFG treatment restored microbial balance, reduced pro-inflammatory cytokines TNF-α, IL-6, and enhanced intestinal barrier integrity by upregulating tight junction proteins ZO-1, Occludin, Calprotectin.Mechanistically, QFG rebalanced Th17/Treg cell ratios and suppressed IL-6/NF-κB signaling, a key driver of muscle atrophy. Combining QFG with glutamine (Gln) further amplified these effects, suggesting synergistic therapeutic potential.Our findings demonstrate that QFG ameliorates cancer cachexia through microbiota modulation and IL-6/NF-κB inhibition, providing a novel multi-targeted approach for cachexia treatment.