Protein carbonylation modification is an irreversible post-translational modification （PTM） that plays a vital role in modulating protein function. The profiling of intracellular protein carbonylation can provide important information for the investigation of the molecular mechanisms of oxidative stress-related protein signaling networks and pathologies of related diseases. Here， we provide a meticulous description and systematic synthesis of recent research progress in protein carbonylation profiling assays development， especially for mass spectrometry-based chemoproteomic platforms for global profiling of protein lipoxidation. Oxidative stress has been regarded as the result of intracellular reactive oxygen species （ROS） exceeding the buffering capacity of antioxidant defenses， triggering oxidative damage towards lipids， DNA， and proteins. Protein carbonylation （PCO） can be produced either directly by amino acid side chain oxidation， protein backbone cleavage pathways， or indirectly via the formation of adducts between protein nucleophilic side chains and lipid peroxidation products or glycosylation products. We focus on the analysis and detection of protein carbonylation caused by lipid-derived electrophiles （LDEs）， and highlight the recent development of protein LDEs profiling assays， especially for mass spectrometry （MS）-based chemoproteomic strategies. Due to the low relative abundance， poor chemical stability， and lack of specific physicochemical properties （e.g. absorption or fluorescence）， many carbonylated proteins could not be detected directly， and their detection and quantification rely on the recognition with specific chemical probes. With these probes， mass spectrometry-based chemo-proteomic platforms emerge as powerful tools for comprehensive profiling of protein carbonylation， offering unparalleled sensitivity and specificity， facilitating the identification of protein targets and modification sites critical for elucidating the molecular mechanisms underlying disease progression.