A series of mononuclear nickel(II) complexes (1–6) have been synthesized from substituted salicylaldehydes containing Schiff bases and characterized by varies spectral methods. The structural parameters of the complexes were evaluated by UV-Vis and DFT calculations, and results indicates square pyramidal (1–3) and octahedral (4–6) geometry around nickel(II) ion. Antimicrobial activity of the complexes exhibits moderate activity, which also exhibit better scavenging activity against ABTS and DPPH methods. In the molecular docking studies, the complexes are showed π–π, σ–π, hydrogen bonding, van der Waals and electrostatic interactions with EGFR kinase receptor. The nickel(II) complexes 2 and 5 show better anticancer activity against MDA-MB-231 cell lines compared to cisplatin and other complexes.