Water recycling and reuse are cornerstones of water management, which can be compromised by the presence of pollutants. Among these, pharmaceuticals can overcome standard water treatments and require sophisticated approaches to remove them. Sorption is an economically viable alternative limited by the need for sorbents with a sorption coefficient (Kd) higher than 500 L/kg. The cross-linking of dextrin (Dx) with divinyl sulfone (DVS) in the presence of 1 mmol or 5 mmol of ibuprofen (IBU) yields the insoluble polymers pDx1 and pDx5 with improved affinity for IBU and high selectivity towards erythromycin (ERY) and ERY Kd higher than 4 × 103 L/kg, when tested against a cocktail of six drugs. Characterization of the polymers shows that both pDx1 and pDx5 have similar properties, fast sorption kinetics, and ERY Kd of 13.3 × 103 for pDx1 and 6.4 × 103 for pDx5, representing 26.6 and 12.0 times the 500 L/kg threshold. The fact that new affinities and improvements in Kd can be achieved by cross-linking Dx in the presence of other molecules that promote pre-organization expands the applications of DVS cross-linked polysaccharides as sustainable, scalable, and environmentally friendly sorbents with a potential application in wastewater treatment plants (WTPs).