A new dialdehyde N, N'-bis(5-formylpyrrol-2-ylmethyl) homopiperazine (A) was synthesized by the Mannich reaction of pyrrole 2-carbaldehyde, formaldehyde and homopiperazine in the presence of hydrochloric acid. From the direct reaction of A with 1,3-diaminopropane or 1,4- diaminobutane two new macrocyclic Schiff base ligands were obtained, L1 and L2, respectively. The reaction of these ligands with Ni(II), Co(II) and Pt(II) metal ions results in formation of the relevant macrocyclic Schiff base complexes. Compounds were characterized by FT-IR, elemental analysis, mass spectrometry, UV-Vis and, in the case of the ligands, by 1H and 13C-NMR. The crystal structure of the complex [Ni2L2(CH3O)]ClO4 (4) showed a binuclear macro-cyclic structure, with each Ni coordinated by three nitrogen atoms from the ligand and by a methoxide bridging the two metal centers. The cytotoxic activities of these compounds indicated that the ligands, and some of the complexes, have high anti-proliferative effect towards A549 and HeLa cells, but not HT29 cells. Pt complex with L1 and L2 displayed stronger anti-proliferative activity toward HeLa (IC50 = 11 µM for both of them and A549 IC50 = 7 µM and 8 µM, respectively) relative to L1 and L2. In addition, the cytotoxic effects of the compounds were assayed in rat fibroblast cells as a model of the normal cell, however none of them showed any significant cytotoxic effects. Thereby upholding the potential of these compounds for further development as chemotherapeutic agents.