Heterocyclic compounds are an integral part of the chemical, life sciences and constitute a considerable quantum of the modern research that is being currently pursued throughout the world. Heterocyclic compounds, having atoms other than carbon in the ring, have long been proven to have vivid biological activities. Thiazolidinone scaffold has become a highly powerful scaffold in the current era when it comes to its clinical importance. Its wide variety of biological functions have piqued the researcher’s intense curiosity. It is a five-membered heterocyclic ring having almost all types of biological activities. A wide range of pharmacological actions, including anti-cancer, anti-diabetic, anti-microbial, anti-viral, anti-inflammatory, and anti-convulsant, are present in thiazolidinones. In the recent years, several innovative synthetic techniques have been developed to create a variety of scaffolds to investigate a range of biological activities. The authors have attempted to summarize various thiazolidinone derivative their synthetic approach as well as their biological importance in this review.