Designing a highly active and selective Se-therapeutic, that mimics the activity of the antioxidant enzyme glutathione peroxidase (GPx), still remains a challenge. Since the discovery of ebselen (N-phenyl-1,2-benzisoselenazol-3(2H)-one) and its ability to act as a GPx mimetic, the search for more effective peroxide scavengers has become a ‘hot topic’ in this field of research. Herein, we present several modifications of the benzisoselenazolone core that enable to improve the antioxidant and anticancer potential of the basic ebselen structure. These transformations include: (a) installation of chiral terpene skeletons, from p-menthane, pinane and carane systems, on the nitrogen atom; (b) exchange of the carbonyl oxygen atom for sulphur to obtain thiocarbonyl derivatives; (c) oxidation of the selenium moiety resulting in a series of benzenoselenenic acids and their further transformation to corresponding water-soluble potassium salts; (d) attachment of an additional phenyl group leading to variously N-substituted unsymmetrical phenylselenides with an o-amido function. All of the synthetized compounds were tested as antioxidants and antiproliferative agents. Conclusions concerning the structure-activity correlation, including the difference in reactivity of specific Se-moieties (-Se-N-, -SeOOH, -SeOOK, -SePh), N-substituents (the influence of bulky aliphatic moiety and the 3-dimensional orientation of atoms), and incorporated heteroatoms (-C=O, -C=S), are presented.