Liquid crystals (LCs) have transformed the world of optoelectronic displays and are now recognized as useful soft materials for a broad range of biomedical applications. Combination of smart sensors with label-free imaging offers intriguing prospects for point-of-care diagnostics. Here, we outline a sophisticated collage of the most important discoveries that show how LC biosensors can be used to monitor different enzymatic activities for the diagnosis of specific disease biomarkers or infections in body fluids, cellular milieu, and clinical samples. In living organisms, enzymes have a primary regulatory role in both accelerating and controlling metabolic reactions. We mention the ubiquitous techniques that are used to fabricate LC-based enzyme biosensors in attaining specific strategies along with greater sensitivity for the detection of clinically important biomolecules.