Recent studies have shown the widespread occurrence of microplastics in multiple environmental compartments. When discharged into the aquatic environment, microplastics interact with other chemicals acting as vectors of organic and inorganic micropollutants. In the present study, we examined the sorption of two commonly used antihypertensive drugs, valsartan (VAL) and losartan (LOS), onto polystyrene (PS) microplastics and we studied the effects of water matrix, solution's pH, salinity, and microplastics' aging on their sorption. According to the results, the sorption of VAL and LOS onto PS is a slow process that reaches equilibrium after 12 days. The sorption of both target micropollutants was pH-dependent and significantly decreased under alkaline conditions. The removal of VAL was enhanced in the presence of 100 mM of Ca²⁺ while no statistical significant effects were observed when Na⁺ was added. The increase of salinity either did not affect or decreased the removal of LOS. Lower sorption of both drugs was observed when aged PS was used despite that the specific surface area for aged PS was 39% higher than pristine. Calculation of the sorption distribution coefficient (K_d) for different water matrices showed that the increase of matrix complexity inhibited target compounds' removal and the sorption rate decreased from bottled water > river water ≈ treated wastewater for the two compounds. For VAL, the K_d values ranged between 795 ± 63 L/kg (bottled water) and 384 ± 88 L/kg (river water), while for LOS between 4453 ± 417 L/kg (bottled water) and 3078 ± 716 L/kg (treated wastewater). Both VAL and LOS sorption onto PS microplastics can be described by hydrophobic and electrostatic interactions. The current results indicate that PS particles could affect the transportation of antihypertensive drugs in the aquatic environment causing potential adverse effects on the environment and public health.