Abstract: Objective: To explore the potential active components and underlying mechanisms of Buzhong Yiqi Decoction (BZYQD) in ameliorating chemotherapy-induced sarcopenia (CIS) through integrated strategies of network pharmacology, molecular docking, and in vivo validation. Methods: The active components of BZYQD and their targets were identified using the TCMSP. CIS-related targets were obtained from the GeneCards and OMIM databases. Construct a PPI network by taking the intersection targets of drugs and diseases and identify the core targets. Perform GO functional annotation and KEGG pathway enrichment. Molecular docking and visualization were performed using AutoDockTools 1.5.7 and PyMOL 2.7.1. Therapeutic effects of BZYQD on CIS were validated in animal experiments. Results: The core targets at the intersection of drugs and diseases, including AKT1, TP53, TNF, IL-1β, IL-6, etc.Molecular docking analysis indicated that the core targets and the main active components exhibited favorable binding affinity. In animal experiments, compared with the control group, the model group showed significant decreases in body weight, grip strength, exhaustive swimming time, and myofiber cross-sectional area. ELISA results indicated that serum levels of TNF-α, IL-1β and IL-6 were significantly elevated.Western blot analysis showed a significant increase in the p-NF-κB p65/NF-κB p65 ratio, while the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased. Administration of BZYQD ameliorated these alterations in a dose-dependent manner, with the high-dose group showing the most pronounced effects. Conclusion: BZYQD may improve CIS by regulating the PI3K/Akt/NF-кB signaling pathway.