Brewer's-spent-yeast (BSY) is among the most voluminous byproducts generated in brewery industry that adds to the waste; however, smart utilization of BSY could lead to edible biomass production besides waste management. To utilize it for biomass production, it is being used in sh feeds; however, its effect on the sh physiology has been scantily studied. The present study investigated the proteomic changes in muscle tissues of carp Labeo rohita fed with BSY-based diet, to understand its impact on muscle physiology and biomass. Six feeds were prepared with different grades of BSY (0, 20, 30, 40, 50, 100% replacement of shmeal with BSY) and shes were fed for 90 days.Highest weight gain%, feed conversion e ciency, speci c growth rate% were observed in 30% BSY-replaced group and this group was considered for the proteomic study. Comparative shotgun proteomic analysis was carried out by LC-MS/MS and data generated have been deposited in ProteomeXchange Consortium with dataset identi er PXD020093. A total of 62 proteins showed differential abundance; 29 increased and 33 decreased in the 30%BSY replaced group. Pathway analysis using IPA and Panther tools revealed that the proteins tyrosine protein kinase, PDGFα, PKRCB and Collagen promote muscle growth by inducing the PI3K-AKT pathway. Conversely, the proteins Serine/threonine-protein phosphatase, Phosphatidylinositol 3,4,5-trisphosphate5-phosphatase 2A, Ras-speci c guanine-nucleotide-releasing factor inhibit muscle growth indicating that 30% BSY replaced feed promote muscle growth in a highly controlled manner. Findings suggest that BSY could be recycled for carp feed production in largescale thereby leading to resource conservation, reducing environmental effects.