The droplet-screen has emerged as an important tool that provides new experimental possibilities for high-throughput biological functional analysis. The continuous generation of large amounts of monodispersed droplets containing a single cell enables effective single-cell isolation for molecule secretion analysis. Based on the advantages of single-cell screening, droplet-based approaches have been conducted for a range of applications in quantitative biology, metabolic engineering and precision medicine. Herein, the recent drop-screen systems are introduced for single-cell functional profiling and sorting. For example, cell-secreted enzymes have been investigated by inserting fluorescence resonance energy transfer (FRET)-based sensors within droplets for screening. A range of engineering enzymes produced by single cells for biological fabrications in the pharmaceutical industry were explored. The capability of biomarker indications allows one to isolate target clonal/mutants, contributing towards engineering biology and clinical treatment strategy.