Disruption of the redox balance in the body causes oxidative stress that can initiate many diseases. While antioxidants reduce the level of oxidizing compounds in the medium, prooxidants promote the opposite process and have been used in therapies in particular those of cancer diseases. In this study, a series of azolyl lactones, were tested in human serum as a biological matrix and the obtained values of their oxy scores (OS) were compared. The antioxidative properties of these compounds were also tested under conditions of induced oxidative stress using an external prooxidant, t-butylhydroperoxide. The results showed that the sulphur analogue 4-azolyl coumarin 5 has the best antioxidant properties (OS ?2.2), while the halogenated derivatives of pyrazolylcoumarin 7 and 8 act as prooxidants, but successfully resist oxidative stress (OS 2.7 and 2.0, respectively). Related phthalides and isocoumarins showed prooxidative properties, but azolyl isocoumarins 10 and 11 show the strongest resistance to oxidative stress, reflected in their negative oxy score value (OS ?2.1 and ?1.1, respectively). The results demonstrated that combining two pharmacophores with known redox properties can produce potent compounds in both directions, with the antioxidative and the prooxidative characteristics.