This study investigated the fate of selected pharmaceuticals and estrogens and the characteristics of bulk organic matter during pellet softening and proposed a possible hybridization with nanofiltration (NF) treatment. A groundwater softening system called pellet softening was used to remove calcium ions from groundwater by crystallizing calcium carbonate on the surface of sand grains that were used as seeding material. This crystallization was confirmed by X-ray powder diffraction, and X-ray fluorescence and scanning electron micrographs were used to characterize the surface of the sand grains during pellet softening. The fluorescence excitation–emission matrix showed that humic-like substances were slightly removed and that specific UV absorbance values decreased after pellet softening. The humic fraction determined by liquid chromatography-organic carbon detection was slightly more attenuated than the fractions of biopolymers, building blocks, low molecular weight acids, and low molecular weight neutrals. Therefore, the aromatic content per unit of dissolved organic carbon was preferentially attenuated during pellet softening. The average removal efficiencies of the three estrogens and 12 selected pharmaceuticals during the softening process were 59 and 5.7%, respectively. However, there was a greater reduction of pharmaceuticals during NF.