In this article we present the synthesis, characterization, and in vitro biological and biochemical activities of new chalcogenozidovudine derivatives as antioxidant (inhibition of TBARS in brain membranes and thiol peroxidase-like activity) as well as antitumoral agents in bladder carcinoma 5637. A prominent response was obtained for the selected chalcogenonucleosides, showing effective antioxidant and antitumoral activities.