In the reprocessing of spent nuclear fuel, nitrogen-donor extractants are more effective in separating actinides and lanthanides. In this article, a series of heterocyclic N-donor ligands with different backbones and different side chain substituents are systematically investigated to analyze their extraction selectivity and complexation abilities for Am(Ⅲ) and Eu(Ⅲ) by using scalar relativistic density functional theory (DFT). Through the analysis of geometric structures and bond properties of the complexes by means of the NBO and QTAIM methods, it was observed that the coordination ability of the N-donor ligand with Am(Ⅲ) was stronger than with Eu(Ⅲ). Thermodynamic analysis showed that these ligands have good extraction ability and separation performance for Am(III) and Eu(III), the backbone and side chain substituents of the ligands and also the organic solvents have significant influences on the extraction selectivity of the ligands for Am(III) and Eu(III) ions. This work provides some theoretical insights for the design of N-donor extractants with good separation performance for lanthanides and actinides.