The DNA origami technique has proven to have tremendous potential for therapeutic and diagnostic applications like drug delivery, but the relatively low concentrations of cations in physiological fluids cause destabilization and degradation of DNA origami constructs preventing in vivo applications. To reveal the mechanisms behind DNA origami stabilization by cations, we performed atomistic molecular dynamics simulations of a DNA origami rectangle in aqueous solvent with varying concentrations of magnesium and sodium as well as polyamines like oligolysine and spermine. We explored the binding of these ions to DNA origami in detail and found that the mechanism of stabilization differs between ion types considerably. While sodium binds weakly and quickly exchanges with the solvent, magnesium and spermine bind close to the origami with spermine also located in between helices, stabilizing the crossovers characteristic for DNA origami and reducing repulsion of parallel helices. In contrast, oligolysine of length ten prevents helix repulsion by binding to adjacent helices with its flexible side chains, spanning the gap between the helices. Shorter oligolysine molecules with four subunits are weak stabilizers as they lack both the ability to connect helices and to prevent helix repulsion. This work thus shows how the binding modes of ions influence the stabilization of DNA origami nanostructures on a molecular level.