Kinetics of substitution reaction of three high spin pyridylmethylene-8-quinolyl iron (II) complexes by CN- ions are studied spectophotometrically in various ratios of aqueous-methanol binary mixtures at 298 ± 0.2 K. Kinetics of the substitution reaction follow the rate law (k2[CN−][complex])on applying of the conditions of the pseudo-first-order. Reactivity of the reaction was investigated in terms of organic ligand moiety and solvent effects. The rate of the reaction increases with increasing of the co-solvent, methanol ratio. This reactivity trend is predominantly due to increasing of the activity coefficient of those hydrophobic complexes in the organic methanol co-solvent depending upon the hydrophobicity of the substituent groups (R) in the coordinated ligand in the complexes. Moreover, reactivity trends of the prepared complexes in the presence of the inserted hydrophobic salts (TBAB, TEAB and TMAB) or hydrophilic salt (KBr) were studied. The observed decrease in the rate constants with increasing salt concentration is due to the cationic character of the reacting complexes. Furthermore, the synthesized complexes exhibited enhanced activity against selected strains of microbes. The ligands and their Fe(II) complexes were screened for anticancer activities against several cell lines of cancer. Furthermore, the antioxidant potential of the presented compounds was studied by applying DPPH assays and showed a potential activity compared with standard Vitamin C. The excellent antimicrobial and anticancer activities of the investigated Fe(II) chelates compared with literature could be promised to be pharmaceutical agents after further studies.