Amphiphilic Janus nanoparticles, which are hydrophilic on one-half of the particle surface and hydrophobic on the other half, are ideal carrier candidates for drug delivery due to their unique physicochemical properties. In this study, we investigate the interactions between amphiphilic Janus nanoparticles coated with hydrophilic and hydrophobic ligands on each half of the surface of the nanoparticle and lipid bilayers with either symmetric or asymmetric leaflet structure and in different phases using atomistic molecular dynamics simulations. The results show that the Janus nanoparticle can easily insert into the liquid-disordered lipid bilayer and asymmetric lipid bilayers with the hydrophobic ligands inserted into the liquid-ordered leaflet. However, the nanoparticle barely inserts into the symmetric liquid-ordered lipid bilayer and tends to be adsorbed onto the surface of the liquid-ordered bilayers with the hydrophilic ligands contacting the surface of the bilayer. The insertion of the nanoparticle is mainly dominated by the hydrophobicity of the ligands, the lipid ordering, and the curvature of the bilayer. Rotation of the nanoparticle only occurs during the initial adsorption process of the nanoparticle onto the surface of the lipid bilayers. This work provides new insight into understanding the interactions of amphiphilic Janus nanoparticles with model biological membranes at the atomistic scale and the application of Janus nanoparticles for drug delivery.