Sulfamethoxazole and its derivatives are commonly utilized in the pharmaceutical and medicinal industry due to their biological and pharmaceutical activities, including anti-tubercular, anti-fungal, anti-cancer, anti-bacterial, and herbicidal activities. This review presents the latest and most promising studies related to synthesizing organic derivatives of sulfamethoxazole and their drug-metal complexes and the biological activity associated with these complexes. Some organic drugs, including sulfamethoxazole, exhibit toxicological and pharmacological properties that can be administered in the form of metal complexes. Many researchers have synthesized organic ligands derived from sulfamethoxazole in the forms of Schiff bases and azo compounds, which exhibited higher biological and industrial properties when compared to sulfamethoxazole alone. One of the essential features that make Schiff base more desirable when used for coordination complexation is that it possesses the ability to coordinate with the metal ions via forming chelating; ring makes them very effective in clinical and analytical applications and represent the latest and most promising studies and relate to synthesizing organic derivatives of sulfamethoxazole and their drug-metal complexes, as well as the biological activity associated with these complexes.