Composts are an emerging biofertilizers used in agronomy that can improve crop performance, but much less is known regarding their modes of action. The current study aimed to investigate the differentially abundant proteins (DAPs) in barley leaves associated with growth promotion induced by application of date palm waste compost. Morphophysiological measurements revealed that compost induced a significant increase in plant height, chlorophyll content, gas exchange parameters and plant biomass. LC-MS/MS analyses indicate that compost induced global changes in the proteome of barley leaves. A total of 62 DAPs (26 upregulated and 36 downregulated) among a total of 2233 proteins were identified in response to compost application. The expression of DAPs was further validated based on qRT-PCR. Compost application showed altered abundance of several proteins related to abiotic stress, plant defense, redox homeostasis, transport, tricarboxylic acid cycle, carbohydrate, amino acid, energy and protein metabolism. Furthermore, proteins related to metabolic processes of phytohormone, DNA methylation and secondary metabolites were induced. These results indicate that barley responds to compost application by complex metabolism pathways and may result in a positive alteration in a physiological and metabolic barley plant state which consequently could lead to improved growth and stress adaptation observed in compost-treated plants.