This work showcased the first physicochemical investigation of Psoralen (PSO) binding to double stranded DNA (dsDNA) through electroanalytical methods, whose results were further explored through a cheminformatic study. Results evidenced that PSO presents one non-reversible anodic peak at E_pa ≈ 1.42 V which is associated with its oxidation and the formation of an epoxide derivative, moreover, PSO analytical signal (i.e. faradaic current) decreases linearly with the addition of dsDNA while the electric potential associated to PSO oxidation shifts towards more positive values, indicating therefore that dsDNA addition hinders PSO oxidation. These findings were corroborated by the chemoinformatic study, which evidenced that PSO intercalates noncovalently between base-pairs of the DNA duplex, and then irreversibly form adducts with both DNA strands, leading up to the formation of a cross-link which bridges DNA helix, what explains the linear dependence between the faradaic current generated by PSO oxidation and the concentration of dsDNA in the test-solution, as well as the dependence between E_p and the addition of dsDNA solution. Therefore, the findings herein reported evidence the applicability of electroanalytical approaches such as voltammetry in the study of DNA intercalating agents.