Lipid droplets (LDs) dynamically interact with other organelles, such as mitochondria, in surveillance of cellular metabolic homeostasis. The transient nature of LDs, however, poses technical challenges to snapshot molecular information underlying these interactions. Herein, we develop a small molecule based photocatalytic protein proximity labeling method (namely LipoID) to in situ label, capture and profile LDs’ interacting proteome. This method is enabled by a set of LDs-targeting probes designed to catalyze protein modifications nearby LDs using nucleophilic substrates. Profiled by LC-MS/MS, LipoID identifies tethered inter-organellar interactions, particularly with mitochondria, besides reliable capture of validated LDs’ biomarkers (e.g. PLINs). Coupled with comparative proteomics, LipoID discovers mitochondrial VDAC3 channel and its inhibitor that regulate the LDs-mitochondria distance. Such inter-organellar regulation was driven by cellular ATP transported through the VDAC3 channel. Further metabolomics analysis revealed remodeled lipid metabolism orchestrated with LDs-mitochondria interaction. Together, LipoID profiles LDs’ interactome and reveals inter-organellar regulation.