Piperidine derivatives (PDs) are novel antioxidants, which have strong abilities to inhibit lipid peroxidation. The experimentally observed activity order of PDs was that SH-substituted PDs>OH-substituted PDs>NH_2-substituted PDs. In order to clarify the structure-activity relationship for PDs, X-H (X=O, N, S) bond dissociation enthalpies (BDEs) for PDs were calculated by density function theory using B3LYP functional on the basis set of 6-31G(d,p). The results showed that the order of X-H BDEs was O-H>N-H>S-H. Taking into account that BDEs are negatively correlated with antioxidant activity, the difference between X-H BDEs, which rises from the differences in the electric negativities of X atoms, successfully elucidated the activity order of PDs. Our finding also implied that in practice OH group can be replaced by SH group to improve the antioxidant activity further. In addition, PDs structures optimized by AM1 were compared with those obtained by B3LYP/6-31G(d,p). It revealed that for OH-substituted PDs, AM1 gave fairly good structures. While for NH2-or SH-substituted PDs, AM1 was not very effective.