Iron is vital and an essential requirement for most plants and animals to maintain the homeostasis of iron through a series of chemical reactions.Normally, the amount of iron in the human body is closely regulated, with a balance being achieved between the amount lost and that absorbed from the diet. Regular blood transfusions in thalassemia and other chronic refractory anemia can result due to the excessive iron deposition in tissues and organs. The regulation of this vital but potentially toxic substance, when present in excessive amounts, can negatively affect several physiological processes in the human body. The present study was conducted to evaluate the compartive efficancy of some natural and synthetic chelating agents towards chelation of iron in the experimental animals. Medicinal plants including amrood (Psidium guajava), green tea (Camella sinesis), turmeric (Curcuma longa) and khatti (Citrus aurentifolia) were evaluated for their natural chelating potential against iron overload in the experimental animals.The extracts from the selected medicinal plants were evaluated for their antioxidant activity, antimicrobial activity, cytotoxicity,along with GC-MS and FTIR phytochemicals profiling. Iron overload was induced by administration of iron sulphate and IROSE (iron sucrose) to the experimental animals. The experiments were conduted to evaluate selective parameters such as serum ferritin, immune status and liver enzymes etc., along with histopathological status of different body organs like liver, kidney and spleen of the model animals. Iron overload caused tissue damage in the experimental animals and also increased the concentration level of biochemical parameters in the serum. The plant derived natural chelating agents/extracts, administrated orally, restored the biochemical parametres and tissue injury of different soft organs of the the experiomnetal animals leading towards the normal state. It can be concluded from the findings of the present study that the tested medicinal plants had appreciable chelation ability to excrete the excess iron from different organs of the thalassaimic patients and thus can be explored as a sustainable source for isolation of natural iron chelating agents to replace the synthetic ones.