Boron neutron capture therapy (BNCT) is considered to have potential for cancer therapy based on the nuclear reaction between boron (10B) atoms and thermal neutrons, yielding 4He2+ (α) and 7Li3+ ions. These heavy particles induce the destruction of biomolecules within short path length of 5–9 μm, resulting in a limited cytotoxic effect to 10B-containing cells. Herein, we report on the design and synthesis of DNA-targeting BNCT agents equipped with homo- and hetero-dimeric macrocyclic polyamine units and their Zn2+ complexes. It was hypothesized that the dizinc(II) complexes of these ligands would recognize two adjacent thymidines (thymidyl(3'–5')thymidine), resulting in an efficient contact with DNA and an efficient breakdown of DNA upon thermal neutron irradiation. To test this hypothesis, we performed a DNA interaction study and a biological evaluation such as cytotoxicity and intracellular uptake activity using cancer and normal cells. BNCT experiments utilizing the corresponding 10B-enriched compounds were also conducted.