Raman spectroscopy is applied in this work to study the adsorption of poly(ethyleneimine) (PEI) on Ag nanoparticles obtained by reduction with citrate. as well as to the study of the interaction between PEI and a plasmid. The surface-enhanced Raman spectroscopy (SERS) affords important information about the interaction and orientation of the polymer on the particles, In particular we have found that this polymer interacts with the surface through their amino groups in an interaction which also involves a change in the protonation state of amino groups, as well as an increase of the chain order, This interaction implies a charge-transfer effect as deduced from the strong resonant effect in Raman spectra obtained at different excitation wavelengths. The complex formed by PEI and a plasmid, obtained by encoding the HBV (hepatitis B virus) genome inside the EcoRI restriction site of pGEM vector, was also studied by SERS. The interaction between both polymers leads to a conformational change affecting both macromolecules that can be detected by Raman at different excitation wavelengths. PEI undergoes a change to a more disordered structure as well as an increase of the number of protonated amino groups. The plasmid undergoes a structural change from A-DNA structure to B-DNA, along with a change in the superhelicity resulting in a more lineal structure when the plasmid interacts with PEI.