This dataset contains LC-MS/MS proteomic data of hybrid biomimetic nanoparticles (MPA NPs) and their source membrane materials, including platelet membrane (PM) and M1 macrophage membrane (MM). MPA NPs are ROS-responsive prodrug nanoparticles coated with fused platelet/M1 macrophage hybrid cell membrane, constructed for targeted therapy of renal fibrosis. The proteomic analysis was performed to characterize the protein composition retained on the hybrid membrane-coated nanoparticles, verifying successful membrane fusion and membrane protein preservation after nanoparticle fabrication. All samples were digested by trypsin and analyzed using Q-Exactive Orbitrap mass spectrometer. Raw mass spectrometry data were searched against the *Mus musculus* UniProt reference database with FDR < 1%. This proteomic dataset reveals the membrane protein profile of MPA NPs, supporting the mechanism that hybrid membrane endows nanoparticles with immune escape and injured kidney targeting capacity.