The present study evaluates the in-vitro cisplatin (CDDP) release from four different poly oxalates cross-linked chitosan (CS) nanocomposites. The poly oxalates were synthesized from the reaction of four different dicarboxylic acids with ethylene glycol (EG). The encapsulation of CDDP on CS cross-linked with Oxalic acid-EG, Succinic acid-EG, Citric acid-EG and tartaric acid-EG carriers were carried out by the ionic gelation technique. The poly-oxalate nanocarriers were characterized by scanning electron microscopy, atomic force microscopy, X-ray diffraction studies and zeta potential analysis. The stability of poly-oxalates was calculated by the density functional theory (DFT) using Gaussview 05. Excellent drug release kinetics and good biocompatibility of nanocomposites were observed for the in-vitro analysis. The unloaded poly oxalate nanocomposites perform to have a low inherent cytotoxicity, whereas the loaded nanocomposites were as active as free CDDP in the MCF-7 cancer cell line. The tumor growth inhibitions of CDDP-loaded nanocomposites are more or equal to that of free CDDP. Taken together, these two poly oxalate nanocomposites are established as promising drug carriers for the delivery of CDDP.