The structural stability of DNA is important because of its biological activity. DNAs due to their inherent chemical properties are not stable in an aqueous solution, therefore, a long period of storage of DNA at the ambient condition in bioscience is of importance. Ionic liquids (ILs) as interesting alternatives compared to organic solvents and water due to their considerable properties can be used as new agents to increase the stability of DNA for a long period of storage. In this article, molecular dynamics (MD) simulations and quantum chemistry calculations were applied to investigate the effects of amino acid ionic liquids ([BMIM][Ala], [BMIM][Gly], [BMIM][Val], [BMIM][Pro] and [BMIM][Leu]) on the dynamical behavior and the structural stability of calf thymus DNA. Based on the obtained MD results ILs enter into the solvation shell of the DNA and push away the water molecules from the DNA surface. Structural analysis shows that [BMIM]+ cations can occupy the DNA minor groove without disturbing the double-helical structure of DNA. ILs due to strong electrostatic and van der Waals (vdW) interactions with the DNA structure contribute to the stability of the double-helical structure. Quantum chemistry calculations indicate that the interactions between the [BMIM]+ cation and DNA structure has an electrostatic character. Moreover, this cation forms a more stable complex with the CGCG region of the DNA in comparison with AATT base pairs. Overall, the results of this study can provide new insight into the application of ILs for maintaining DNA stability during long-term storage.Communicated by Ramaswamy H. Sarma.