Schiff bases demonstrate biological activities and are unexacting to synthesize, which makes them attractive platform for drug discovery. This article, includes synthesizing and assessing urease inhibitory activity of Schiff base metal complexes. The Schiff base ligands were synthesized by condensing ketones or aldehydes (carbonyl compound) with specified amines and thereafter coordinating them with transition-metal ions like as nickel(II), cobalt(II), copper(II), and zinc(II), followed by their spectroscopic characterization. In vitro, evaluation of Schiff base and their complexes was done using thiourea as the reference. Many of the synthesized metal complexes demonstrated marked suppression of urease activity, emphasizing their promise for pharmaceuticals. Incorporation of electron-withdrawing substituents, results in enhancement of inhibitory potency of these complexes. These outcomes indicate that Schiff base metal complexes are promising lead structures for the development of new urease inhibitors aimed at managing urease-mediated conditions, including gastric ulceration and urinary tract infections.