The study investigates the efficiency of air-gap membrane distillation (AGMD) in water recovery and antibiotics removal from wastewater, focusing on high-concentration scenarios. Experimental findings reveal enhanced membrane performance with increasing the feed temperature, resulting in vapor permeate fluxes of up to 5 kg/m2.h at higher temperatures. Despite experiencing flux reduction caused by fouling from humic acid (HA) in the feed antibiotics solution, the antibiotics consistently maintain near-complete rejection rates (>99%) over 48 h. The foulant on the membrane surface was illustrated by SEM imaging. To know the temperature polarization and the fouling resistance, mathematical modeling was used, and it validates experimental results, elucidating temperature polarization effects and mass transfer coefficients. An increase in feed flow rates reduced thermal boundary layers, enhancing heat flux. Higher temperatures reduced HA fouling resistance. Therefore, AGMD proves effective in water recovery and antibiotics removal, with mathematical models aiding fouling understanding for future research and detailed computational fluid dynamics (CFD) models.