Smart microgels can be used as sorbents, possessing high surface area and rapid stimuli‐responsiveness. A series of poly(N‐isopropylacrylamide) (pNIPAM) and pNIPAM‐co‐starch nanoparticles (pNIPAM‐co‐SNPs) thermo‐responsive microgels were synthesized, presenting different hydrophilic/hydrophobic behavior according to the composition. The adsorption studies were carried out for methylparaben (MPB), ethylparaben (EPB), propylparaben (PPB), butylparaben (BPB), and bisphenol A (BPA), and the extraction and desorption efficiency were determined by high‐performance liquid chromatography and spectrophotometric detection (HPLC‐UV). The effect of microgel phase transition according to the temperature and the copolymerization with SNPs in each sorptive step was investigated. The extraction of less polar compounds (BPA, PPB, and BPB) above the volume phase transition temperature (VPTT) was favored, driven by a predominant hydrophobic interaction. According to microgel composition, the desorption capacity as a function of temperature can be influenced by hydrophilic interactions and water competition. Molecular dynamics (MD) simulations and binding free energy calculations were performed to provide theoretical evidence about binding energies between pNIPAM and BPA, which experimentally showed the best extraction efficiency results. These findings may provide a strategy for designing high‐performance sorptive phases that could remove hydrophilic and hydrophobic compounds from water and a hypothesis about the driving forces of such processes.