A series of condensed Imidazo [2, 1-b] [1,3] thiazole Chalcones have been synthesized by Claisen-Schmidt condensation reaction. Imidazo thiazole Chalcones are associated with immense biological activities. Novel Imidazo thiazole-based chalcones were synthesized using Imidazo thiazole-3carboxaldehydes and various acetyl ketones in PEG-400. The structures of the compounds were characterized by IR, 1 H NMR and screened for their in-vitro antioxidant (DPPH and SOD) activity. DPPH free radical scavenging activity was given by the compounds 7a-j at with (0.5 mmol/L in methanol). The compounds having substituent hydroxyl, fluoro, methoxy, ethoxy, and fluoro as well as benzimidazole and a ferrocenyl moiety in chalcone structure (7a-j) shows enhancement in antioxidant activity. Particularly in compounds like 7e, 7f, 7g, and 7h show the moderate percentage and 7c show the strongest percentage of inhibition mainly at (C=1mM). Almost all the compounds indicate moderate to good antioxidant activity compared to that of standard ascorbic acid percentage antioxidant activity (1 mm) by DPPH and SOD as 44.18 and 74.07 respectively. The resultant absorbance was recorded at 517 nm after 30 min incubation at 37 ºC. It was also found to be a potent scavenger of SOD, and this property may be responsible for the good anti-inflammatory activity of corresponding Imidazo-Thiazole Chalcones. Almost all the synthesized novel Imidazothiazole chalcones show potent antioxidant activity.