Herein, we report the anti-malarial, anti-bacterial and anti-inflammatory activities of the N₂O₂ donor tetradentate salen type ligand and its CoL, NiL, and CuL metal complexes. The synthesized compounds were characterized by various spectroscopic analytical methods. The in-vitro anti-malarial investigations revealed that the complex CuL exhibited equipotency with quinine drug having IC₅₀ value 0.25 μg/mL. The compound L showed significant inhibition of bacterial spp. viz. E. Coli, P. Aeruginosa, and S. Aureus (MIC=12.5–50 μg/mL), while the compound CoL (MIC=12.5 μg/mL) exhibited potency against gram-positive bacteria. In the in-vitro anti-inflammatory study, the compound CuL displayed moderate activity than other tested compounds. The compound CuL showed the highest anti-malarial docking score with enzyme pLDH at −8.12 Kcal/mol. The DFT study also gives authentication of higher antimalarial activity of CuL due to high dipole moment. None of the potent compounds was found cytotoxic towards vero cell lines.