Emerging evidence indicates that lipid droplets (LDs) play important roles in lipid metabolism, energy homeostasis, and cell stress management. Notably, dysregulation of LDs is tightly linked to numerous diseases, including lipodystrophies, cancer, obesity, atherosclerosis, and others. The pivotal physiological roles of LDs have led to an exploration of research in recent years. The functions of LDs are inherently connected to the composition of their proteome. Current methods for profiling LD proteins mostly utilize LD fractionation, including those based on proximity-based labeling techniques. Global profiling of the LD proteome in live cells without the isolation of LDs is still challenging. Herein, we disclose two small-molecule chemical probes, termed