In current review, authors aim to inspire the researcher through structure activity relationship strategy for the finding of safe and effective anticancer molecules. Nowadays cancer is measured as one of the major health problems in human beings in the world from decades. A classes of heterocyclic compounds have been recognized through molecular biology, empirical screening and rational drug development for the evaluation of anticancer molecules however regrettably, till now we could not find a medicine to be entirely active and nontoxic for the treatment of cancer patients. In pointed view, it might be measured that Thiazolidinedione (TZD) heterocyclic compounds are prodigious standing in the synthetic and pharmacological approach of medicinal chemistry. Thiazolidinedione (TZD) nucleus upon the substitution of various functional groups is provides a wide spectrum of biological activity by the use of different mechanism on different target sites. Recently, some of the substituted thiazolidinedione molecules are designed for the treatment of human cancers cell line through different molecular mechanism such as EGFR & Mushroom Tyrosine kinase inhibitor, COX enzyme inhibitors, Histone deacetylase inhibitors, Alpha glucosidase inhibitor, DNA intercalation and Protein tyrosine phosphatase 1B (PTP1B) inhibitor, basically in which PPAR gamma express are in high levels. Peroxisome proliferator-activated receptor (PPAR) gamma ligands effect on apoptosis, cell proliferation and cell differentiation on different types of cell. The most commonly cascades in human cancers cell are Raf/MEK/ERK, Wnt and PI3/Akt. This article highlights and embraces a concise overview of recent approaches for the synthesis of new thiazolidinedione molecules with its structure activity relationship strategy and effects on various signaling pathways, which is responsible for the expresses of cancer cell line activity.