Conventional high throughput methods assaying the chemical state of water and the risk of heavy metal accumulation share common constraints of long and expensive analytical procedures and dedicated laboratories due to the typical bulky instrumentation. To overcome these limitations, a miniaturized optical system for the detection and quantification of inorganic mercury (Hg2+) in water was developed. Combining the bioactivity of a light-emitting mercury-specific engineered Escherichia coli—used as sensing element—with the optical performance of small size and inexpensive Silicon Photomultiplier (SiPM)—used as detector—the system is able to detect mercury in low volumes of water down to the concentration of 1 µg L−1, which is the tolerance value indicated by the World Health Organization (WHO), providing a highly sensitive and miniaturized tool for in situ water quality analysis.