Mesoionic compounds are dipolar five or six membered heterocyclic compounds containing both the delocalized negative and the positive charge, for which a totally covalent structure cannot be written and which cannot be represented satisfactorily by any one polar structure. The most important member of mesoionic category of compounds is the sydnone ring system. Sydnones are mesoionic compounds having the 1, 2, 3-oxadiazole skeleton and unique variation in electron density around the ring. These characteristics have encouraged extensive study of the chemical, physical, and biological properties of sydnones, as well as their potential application as antioxidants. This chapter covers synthesis and antioxidant activity of most potent molecules having sydnone ring. Most potent antioxidant molecules are 3-(2-carboxyphenyl) sydnone, 3-(2,4-dimethoxy-5-chlorophenyl) sydnone have IC50(μM) values are 0.11 and 0.16 respectively. Similarly compounds 4-[1-oxo-3-(4-chlorophenyl)-2-propenyl]-3-(4- fluorophenyl) sydnones, 4-[1-oxo-3-(4-N-dimethylphenyl)-2-propenyl]-3-(4-fluorophenylsydnones, 4-[1-oxo-3-(4-Ndimethylphenyl)- 2-propenyl]-3-(4-chlorophenyl) sydnones, 4-[1-oxo-3-(4-chlorophenyl)-2-propenyl]-3-(4- chlorophenyl) sydnones are highly potent antioxidant activity with IC50 (μM), values are 4.18, 5.12, 4.15. and 4.26 respectively. This delivers focus of future research in the development of potent antioxidant sydnone molecules. It will be used to design and development of structurally modified antioxidant sydnone derivatives to explore more potent antioxidant biodynamic molecules.