Phenotyping single cells based on molecules that they secrete or consume is a key bottleneck in many biotechnology applications. Here, we demonstrate a new approach for detecting secretions from individual single cells, namely, plasmonic colloidosome-based single cell detector (PCSD). This strategy uses colloidosomes to encapsulate single cells and aid molecular detection. Colloidosomes are constructed by emulsifying lactate probe and hydrophobic ligand dual-functionalized silver nanoparticles on an immiscible liquid-liquid interface. The established colloidosome-based platform exhibits negligible surface-enhanced Raman scattering (SERS) background interference, ultrasensitive SERS response, and excellent signal reproducibility in response to acidification of the medium inside the colloidosomes. Taking lactate as a model molecule, the acidification induced by single cells confined in the colloidosomes is detected. The approach shows promising applicability in single cell analysis based on extracellular metabolites production or consumption.