We present a portable microsystem to quantitatively detect cocaine in human saliva. In this system, we combine a microfluidic-based multiphase liquid–liquid extraction method to transfer cocaine continuously from IR-light-absorbing saliva to an IR-transparent solvent (tetrachloroethylene) with waveguide IR spectroscopy (QC-laser, waveguide, detector) to detect the cocaine on-chip. For the fabrication of the low-cost polymer microfluidic chips a simple rapid prototyping technique based on Scotch-tape masters was further developed and applied. To perform the droplet-based liquid–liquid extraction, we designed and integrated a simple and robust droplet generation method based on the capillary focusing effect within the device. Compared to well-characterized and commonly used microfluidic H-filters, our system showed at least two times higher extraction efficiencies with potential for further improvements. The current liquid–liquid extraction method alone can efficiently extract cocaine and pre-concentrate the analytes in a new solvent. Our fully integrated optofluidic system successfully detected cocaine in real saliva samples spiked with the drug (500 μg/mL) and allowed real time measurements, which makes this approach suitable for point-of-care applications.