A clean and efficient route was established to synthesize sulfonamido-thiocarbamides via one-pot reactions in aqueous medium without use of a catalyst and/or organic solvent. The reaction with stoichiometric molar portion could be carried out in an open atmosphere to offer sulfonamido-thocarbamides in good to excellent yields and purities. The novel and clean methodology offers the advantages including short reaction time, excellent yields, operational simplicity, less leaks and environmentally benign path. The identity of newly synthesized compounds is based on elemental and spectral data. They have been further screened for their microbiological activities.