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Background: A new class of 5-(styrylsulfonylmethyl)-1,3,4-oxadiazol-2-amine and 5- (styrylsulfonylmethyl)-1,3,4-thiadiazol-2-amine derivatives were prepared by derivatization of amino function. Methods: All the synthesized compounds were tested for antioxidant and anti-inflammatory activities. Results: The 2-amino-3-chloro-N-(5-(4-methylstyrylsulfonylmethyl)-1,3,4-oxadiazol-2-yl)-propanamide (12b) and 3-chloro-N-(5-(4-methylstyrylsulfonylmethyl)-1,3,4-oxadiazol-2-yl)-butanamide (14b) displayed significant antioxidant activity, greater than the standard Ascorbic acid. Conclusion: Moreover, 12b and 14b also exhibited promising anti-inflammatory activity.