Identification of biomolecule interactions is crucial in understanding biological and biochemical processes. This review presents a brief outline of the advances in microfluidic chips devoted to biomolecule interactions. Various separation modes used for biomolecule interactions are discussed first, in which microchip isoelectric focusing, microchip zone electrophoresis, microchip electrophoresis frontal analysis, and T-sensor microfluidic channel are included. Detection methods on these microsystems are essential for the identification and quantification of chemical species and biomolecule that are being analyzed. Within the detection methods section, time-resolved resonance raman spectroscopy, mass spectrometry, surface plasmon resonance imaging, deep UV laser-induced fluorescence, indirect laser-induced fluorescence, contactless conductivity detection techniques are discussed. Applications including biomolecule interaction kinetics, protein-protein interaction, protein-DNA interaction, drug-protein interaction, and drug-DNA interaction are outlined. To our knowledge, biomolecule interactions studying microfluidic chip have not been reviewed before.