Theoretical calculations on interaction of the C20 fullerene (consists solely by pentagons) with the smallest amino acid (glycine) were carried out using density-functional theory method. The glycine molecule energetically prefers to interact with the Top-site on the C20 cage via its amino nitrogen (N) active site. The stable ordering of three active sites on glycine molecule is NH2-site > O-site > OH-site. Moreover, when the Gd atom is encapsulated to the center of C20-glycine, the cage volume obviously increase ∼24.8%; and the endohedral atom induces the generation of two strong bands in the partial density of states spectra, which could cause the effect on optical properties. Additionally, it is also found that the modified C20-glycine derivative by Gd atom can reduce the thermodynamic and kinetic stabilities. It could be expected that the study may provide a theoretical reference in exploring their intrinsic feature structurally to antitumor activity. © 2012 Wiley Periodicals, Inc.