The presence of both sp1- and sp2-hybridized carbon atoms in graphyne (GY), a nanomaterial resembling the 2D graphene, has led researchers to speculate possible outstanding properties of this material. Recent studies have also been successful in synthesizing derivatives of GY, such as graphdiyne (GY-2), which holds promises in various applications, notably biomedicine. In anticipation of successful synthesis and wide applications of GY as a novel 2D nanomaterial in the near future, we utilized in silico molecular modeling to examine and predict the material's potential impacts while placed in a biological system, in particular its interactions with cell membranes. Intriguingly, we found that while in the vicinity, GY can be spontaneously inserted into POPC membrane and extract large amounts of phospholipids from it. When compared with graphene, GY shows a relatively weaker capability of lipid extraction though, which is also confirmed by free energy perturbation (FEP) calculations where the POPC lipid molecule shows a larger reduction in free energy when being extracted from the membrane to the graphene surface than to the graphyne surface. This difference in lipid-extraction capability was mainly due to the significantly different carbon density in nanosheets.