The sulfamethizole antibiotic drug has rich hydrogen bond functionalities (donors: amine NH 2 and imine NH; acceptors: sulfonyl O, thiazolidine N and S, and imidine N) which makes it a functionally diverse molecule to form cocrystals. A cocrystal screen of sulfamethizole (SMT) with COOH, NH 2 , pyridine and CONH 2 functional group containing coformers, e.g.paminobenzoic acid (PABA), vanillic acid (VLA), p-aminobenzamide (ABA), 4,4-bipyridine (BIP), suberic acid (SBA), oxalic acid (OA), and adipic acid (ADP), resulted in six cocrystals and one salt namely, SMT-ADP (1:0.5), SMT-PABA (1:1), SMT-VLA (1:1), SMT-ABA (1:1), SMT-BIP (1:1), SMT-SBA (1:0.5), and SMT-OA (1:1). The novel crystalline adducts were synthesized by liquid-assisted cogrinding and isothermal solvent crystallization. In addition to single-crystal X-ray diffraction, the phase composition of the powder samples was confirmed by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Hydrogen bonding interactions between the coformers and SMT are analyzed as six different synthons. In addition to strong N-H···O and O-H···N H-bonds, the cocrystal structures are sustained by weak C-H···O hydrogen bonds. The not so common chalcogen-chalcogen (S···O) type II intermolecular interaction in SMT-ADP cocrystal and chalcogen-nicogen (S···N) type II interaction in SMT-BIP cocrystal were observed. The products were characterized by vibrational spectroscopy to obtain information on the strengths of the intermolecular interactions. Solubility and dissolution experiments on SMT-ADP, SMT-SBA and SMT-OA showed lower intrinsic dissolution rate (IDR) and equilibrium solubility compared to SMT in 0.1N HCl medium, which is ascribed to stronger N-H···O, N-H···N, and O-H···O hydrogen bonds and better crystal packing. The decreased IDR could be useful in controlled/extended release of SMT to improve therapeutic activity of the drug by minimizing its fast systemic elimination in vivo. Furthermore, we observed that SMT-OA salt is formed spontaneously when the components were mixed in acidic medium (0.1N HCl), whereas in neutral medium (phosphate buffer) no SMT-OA salt formation was observed.