Heterocycles are important structural components in pharmacophores that are currently being used to treat several diseases. Among the various heterocyclic scaffolds, nitrogen and sulfur containing spiroheterocycles are essential structural motifs that constitute diverse biodynamic agents. In the last two decades, a paradigm shift has occurred in the synthesis of spirothiazolidin‐4‐ones by replacing conventional and multi‐step synthesis with green protocols, that use novel organo and nanocatalysts. In this review, literature on spirothiazolidin‐4‐ones from years 2000–2021 has been summarized into groups of different synthetic strategies and their potential biological activities. In this review, new developments in the synthetic strategy and biological profile of spirothiazolidin‐4‐ones have been reviewed from years 2000 to 2021. Literature on spirothiazolidin‐4‐ones for past 20 years has been summarized and categorized.