Non Steroidal Anti-inflammatory Drugs (NSAIDs) form the most common class of anti-inflammatory and analgesic agents. They also show anticancer properties for which they exert their effects by interacting at the protein but not at the genomic level. This is because most NSAIDs are anions at physiological pH, which prohibit their approach to the polyanionic DNA backbone. Complexing NSAIDs with bioactive metal like copper obliterates this disadvantage. Here, copper complexes of two oxicam NSAIDs, Lornoxicam (Lx) and Isoxicam (Isx) have been chosen to study their interaction with calf thymus (ct) DNA and have been synthesized as per reported protocols. UV–vis absorption showed that DNA binding to Cu(II)-Lx complex alters the absorption spectra indicating changes in the electronic environment of the complex, whereas, for Cu(II)-Isx there was only small changes. Hence, UV–vis absorption was used to determine the binding constant, stoichiometry and thermodynamic parameters of Cu(II)-Lx. However, UV-melting studies and CD difference spectra showed that both Cu(II)-Lx and Cu(II)-Isx can interact with the DNA backbone albeit with different binding modes. The probable binding mode was determined by kinetics of EtBr displacement and viscosity measurements. Our results point to an intercalative mode of binding for Cu(II)-Lx and external groove binding for Cu(II)-Isx. © 2016 Elsevier B.V.