Objective To explore the potential active components and underlying mechanisms of Buzhong Yiqi Decoction ( BZYQD) in ameliorating chemotherapy-induced sarcopenia ( CIS) using integrated strategies of network pharmacology and in vivo validation. Methods The active components of BZYQD and their targets were identified using the TCMSP platform. CIS-related targets were obtained from the GeneCards and OMIM databases. We constructed a protein-protein interaction network by taking the intersection targets of drugs and diseases and identifying the core targets. We carried out gene ontology ( GO) functional annotation and kyoto encyclopedia of genes and genomes pathway ( KEGG) enrichment. Molecular docking and visualization were performed using AutodockTools 1. 5. 7 and PyMOL 2. 7. 1. The therapeutic effects of BZYQD on CIS were validated in animal experiments. Results The core targets at the drugs/ diseases intersection included Akt1, TP53, tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6. Molecular docking analysis indicated that the core targets and main active components had favorable binding affinities. In the experiment on SD rats, body mass, grip strength, exhaustive swimming time, and myofiber cross-sectional area were significantly decreased in the model (M group) compared with the control group (C group). Serum levels of TNF-α, IL-1β, and IL-6 detected by enzyme-linked immunosorbent assay were significantly elevated. The phospho (p)-nuclear factor (NF)-κB p65/ NF-κB p65 ratio was significantly increased, while the p-Akt /Akt and p-phosphoinositide 3-kinase ( PI3K) / PI3K ratios were significantly decreased, as shown by Western Blot.Administration of BZYQD ameliorated these alterations in a dose-dependent manner, with the most pronounced effects in the HBYD group. Conclusions BZYQD may improve CIS by regulating the PI3K/ Akt / NF-κB signaling pathway.