The constant accumulation of antibiotics and their degradation products in wastewater as a result of human activity poses a serious threat to humanity and other living beings. To contribute to solving this important problem, hollow hexagonal boron nitride nanoparticles (BNNPs) with a spherical shape and smooth surface were synthesized, which were characterized as an efficient adsorbent for wastewater treatment from three types of antibiotics: ciprofloxacin (CIP), tetracycline (TC), and benzylpenicillin (BP). As follows from DFT calculations, the interaction of antibiotic molecules (AM) with the BN surface is neither purely physical nor purely chemical, and negative binding energy (BE) indicates that the adsorption process is spontaneous and endothermic. The calculated electron density redistributions at the AM/BN interfaces show that antibiotics interact with BN mainly through oxygen-containing groups. In addition, this interaction causes the BN surface to bend, which increases both the BE and the contact area. The removal efficiency of antibiotics (Re, %) depends on their initial concentration. At an initial concentration of 10 µg/mL, Re50 and Re100 were observed after 24 h and 14 days, respectively. With an increase in the initial concentration to 40 μg/mL, Re50 and Re100 were achieved after 5 and 28 days (with the exception of ciprofloxacin (~80% Re)). The maximum sorption capacity of BNNPs (qe) was determined to be 297.3 mg/g (TC), 254.8 mg/g (BP), and 238.2 mg/g (CIP), which is significantly superior to many other systems. Tetracycline is adsorbed much faster than the other two antibiotics, which is confirmed by both theoretical and experimental data. Based on the results of the DFT analysis, a simple and efficient sorbent regeneration strategy was proposed, which ensures complete removal of antibiotics after 14 (BP), 21 (TC), and 10 (CIP) days. Thus, the obtained results clearly show that BNNPs are promising sorbents for various classes of antibiotics, including aminoglycosides, tetracyclines, and β-lactams.