Increasing contamination of wastewater with antibiotics used in agriculture, animal husbandry, and medicine is a serious problem for all living things. To address this important issue, we have developed an efficient platform based on a high specific surface area hexagonal boron nitride (BN) coating formed by numerous nanopetals and nanoneedles. The maximum sorption capacity of 1 × 1 cm2 BN coatings is 502.78 µg/g (tetracycline, TET), 315.75 µg/g (ciprofloxacin, CIP), 400.17 µg/g (amoxicillin, AMOX), and 269.7 µg/g (amphotericin B, AMP), which exceeds the sorption capacity of many known materials. Unlike nanoparticles, BN-coated Si wafers are easy to place in and remove from antibiotic-contaminated aqueous solutions, and are easy to clean. When reusing the adsorbents, 100% efficiency was observed at the same time intervals as in the first cleaning cycle: 7 days (TET) and 14 days (CIP, AMOX, AMP) at 10 µg/mL, 14 days (TET, CIP, and AMOX) and 28 days (AMP) at 50 µg/mL, and 14 days (TET) and 28 days (CIP, AMOX and AMP) at 100 µg/mL. The results obtained showed that TET and CIP are best adsorbed on the surface of BN, so TET was chosen as an example for further theoretical modeling of the sorption process. It was found that adsorption is the main mechanism, and this process is spontaneous and endothermic. This highlights the importance of a high specific surface area for the efficient removal of antibiotics from aqueous solutions.