This review summarizes advancement in the field of pyridyl-based organochalcogen ligands in terms of their coordination behavior and biological applications. Pyridylchalcogen chemistry is well researched with reference to various technological applications but the targeted biological applications of this class of high utility ligands have not been well documented, and therefore, not fully understood. At the same time, the role of ligand-associated coordination chemistry and related mechanisms that exhibit remarkable biological performance is yet not explored. This comprehensive review projects the potential of pyridyl-based organochalcogen ligands and its metal complexes for varied biological applications, including antioxidant, antimicrobial, antiviral, anticancer, anti-inflammatory and enzyme inhibitor properties. This review will serve as an essential guideline to understand and explore the biological activity of project pyridyl-based chalcogen ligands and their metal complexes.