This study explores the structural, electronic, and biological properties of ten copper(II) complexes with Schiff bases (N,N′-bis(5,5′-R-salicylidene)-1,4-butanediamine)) ([Cu2(MeO-L1)2], [Cu2(Me-L2)2], [Cu(H−L3)], [Cu(Cl-L4)] and [Cu(NO2-L5)]), and their hydrogenated ligands (N,N′-Bis(5,5′-R-salicyl)butylenediamine) ([Cu(MeO-LH1)], [Cu(Me-LH2)], [Cu(H−LH3)], [Cu(Cl-LH4)] and [Cu(NO2-LH5)]). The complexes were characterized by, elemental analysis, IR, Uv-vis, mass spectrometry, EPR, and cyclic voltammetry. The crystal structure of [Cu2(MeO-L1)2], [Cu2(Me-L2)2], and [Cu(H-L3)] were determined via single crystal X-ray diffraction, revealing orthorhombic and monoclinic systems with space groups P21, C2221, and Pbca, respectively. X-ray diffraction, also, confirmed distorted square-planar geometries for the complexes. EPR spectra, recorded in DMSO solution at 77 K, indicated axial anisotropy and confirmed distorted square-planar geometries for most complexes and suggested a covalent character in metal-ligand bonding. Cyclic voltammetry revealed reversible redox behavior for Schiff base complexes and irreversible processes for hydrogenated ligands, with electron-withdrawing substituents favoring reduction processes. The results demonstrate the significant influence of ligand flexibility and substituent effects on the electronic properties and coordination geometry of the complexes, with electron-withdrawing groups favoring reduction processes. Biological assays demonstrated that [Cu2(Me-L2)2] and [Cu(Cl-LH4)] exhibited significant antiproliferative activity against A549 and HeLa cancer cell lines, surpassing cisplatin in efficacy. The leishmanicidal activity of [Cu(Cl-LH4)] and ligands H-L3, H-LH3 and Cl-LH4 showed potent inhibitory effects on Leishmania mexicana, with no cytotoxicity on RAW 264.7 macrophages. These findings underscore the potential of these copper(II) complexes for therapeutic applications, influenced by ligand flexibility and substituent effects.