Hydrogen sulfide (H 2 S) is the third endogenous gas in mammals that plays an important role in understanding human physiological and pathological processes. However, it remains difficult to measure H 2 S in living biological specimens due to interference of other biothiols (GSH, Cys, Hcy, and thiol-containing proteins) as well as low concentrations of H 2 S (as low as sub-nM). Here, we present Au@AgI core−shell plasmonic nanoparticles (PNPs) as highly sensitive probes to acquire sulfide rapid monitoring in biological environments. When the Au@AgI PNPs are exposed to sulfide, the AgI transforms into Ag 2 S, leading a change of local surface plasmon resonance (LSPR), thereby resulting in a color and light intensity change at the single nanoparticle level which can be monitored by dark-field microscopy (DFM). This strategy has an ultralow limit of detection (LOD) of 33 pM and great antiinterference ability for sulfide detection in biological environments. This method was successfully used for highly sensitive sulfide mapping in live cells and to record the changes of H 2 S levels in different brain regions of rats during acute cerebral ischemia, validating that this method suitable for trace sulfide sensing in biological environments. We anticipate that this sulfide sensor has potential applications for studying complex neurochemical changes.