Lipid-derived electrophile (LDE) modifications, which are covalent modifications of proteins by endogenous LDEs, are essential types of protein posttranslational modifications. LDE modifications alter the protein structure and regulate their biological processes in cells. LDE modifications of proteins are also closely associated with several diseases and function as potential biomarkers for clinical diagnosis. The crucial step in studying the LDE modifications is to enrich the LDE modified proteins/peptides from complex biological samples with high efficiency and high selectivity and quantify modified proteins/peptides with high accuracy. In this review, we summarize the recent progress in MS-based proteomic technologies to globally identify and quantify LDE modified proteomes, mainly focusing on discussing the qualitative and quantitative technologies.