Among the multifarious approaches to treat health challenges such as microbial infections, cancers, and diabetes, metallotherapy is a very significant one. Many transition metal‐based candidates have been previously developed that displayed promising therapeutic interests. Vanadium is one such biologically important transition metal, and in the present work, we have developed potent bioactive vanadium complexes, namely, [{VVO(hpdbal‐smdt)}2μ‐O] (1), [VVO(hpdbal‐smdt)(bha)] (2), [VVO(hpdbal‐smdt)(cat)] (3), [VIVO(hpdbal‐smdt)(phen)] (4), and [VIVO(hpdbal‐smdt)(bipy)] (5), which were synthesized using a ONS donor‐based ligand, H2hpdbal‐smdt (H2L), and [VO(acac)2] alongside secondary ligands, benzohydroxamic acid (bha), catechol (cat), 1,10‐phenanthroline (phen), and 2,2′‐bipyridyl (bipy), respectively. The complexes were mainly characterized using electron paramagnetic resonance (EPR), 1H‐NMR, 13C‐NMR, and infrared (IR) spectroscopy techniques. The ligand was additionally characterized using a single‐crystal X‐ray diffraction (XRD) technique. The compounds were tested for their therapeutic versatility, namely, glucose uptake activity, free radical scavenging activity, and growth inhibitory action towards resilient microbial strains and liver cancer cells. The oxo‐bridged dinuclear vanadium complex (1) showed promising growth inhibitory activity against Pseudomonas aeruginosa bacterial species. Secondary ligand tethered compound (2) displayed notable toxicity against the human liver cancer cells. All complexes induced glucose uptake by the insulin‐resistant cells and exhibited moderate to high antioxidant potential. pH titration and interaction study of these complexes with bovine serum albumin were conducted to investigate solution stability and protein binding properties.