Liquid crystals (LCs) based biosensors are promising systems to detect several bioanalytes and diseases as they are simple yet highly sensitive, and low-cost. These biosensors are based on the ordering transformations of LC molecules due to the specific binding of molecules. In this article, we present the principle and fabrication process of LC-based biosensors and their signal detection by probing different interfacial interactions. Compared to conventional biosensors available, LC-based biosensors provide rapid, cost-effective, and selective detection of various chemicals and biological analytes for better healthcare.