<p>Isatin and its derivatives are very useful in heterocyclic frameworks commonly applied in medicinal chemistry, materials science, and organic synthesis, as they have a wide range of biological and pharmacological applications. Traditional synthetic methods tend to be based on the use of toxic solvents, severe reaction conditions, and high-priced catalysts, posing environmental and economic challenges. Conversely, MNPs-catalyzed processes are a greener approach due to the low toxicity, abundance, low cost, and high catalytic rate of iron. The review speaks of different solvent-free methods that increase the rate of the reaction, selectivity, and yield with less formation of waste. The summary of the mechanisms of Fe NP catalysis and surface activation mechanisms is outlined to determine why the catalysis is more efficient in solvent-free conditions. Multicomponent and one-pot reactions are considered particularly in the context of rapid isatin derivatization. The importance of nanoscale effects on catalyst recyclability and stability is also discussed. As compared to other metal nanocatalysts, it can be demonstrated that iron-based systems are advantageous when it comes to green chemistry. These methods are assessed in terms of their industrial and pharmaceutical significance. Existing restrictions and issues regarding catalyst recovery and scalability are discussed. The future visions are on magnetically recoverable Fe NPs and hybrid nanocatalysts. In general, the solvent-free synthesis using Fe NPs is a prospective green system of sustainable isatin chemistry.</p> Graphical abstract <p></p>