Contemporary pharmaceutical chemistry faces several challenges in different directions, including the need for both the potency and specificity of any therapeutic agent. The increasingly demanding low toxicity requirements observed in all patients treated and the need for novelty in intellectual property, given the extensive use of benzenoid and heteroaromatic ring systems in many patents. Such challenges are increasingly met by moving to new and / or unusual ring systems (scaffolds) that lie outside the realm of (hetero) aromatic systems. This critical review examines the biological activities of Thiazolidine derivatives like anti-microbial, anti-cancer, anti-diabetics, antiobesity, anti-oxidant by giving mechanistic insights of the given atypical scaffolds from mainly drawn from the literature of the last five years, which have found applications in modern bioorganic chemistry and Medicinal Chemistry.