Antibiotics generally cause drug-resistant genes (ARGs) and drug-resistant bacteria (ARBs). With a complex class of antibiotics, it is very crucial to select specific adsorbents for different kinds of antibiotics. Zn-Al layered double hydroxide (LDH) and calcined layered double hydroxide (LDO) were prepared as absorbents for tetracycline hydrochloride (TCH) and ofloxacin (OFX), which were two antibiotics with different structures. According to the results of the adsorption experiments, LDO has the best adsorption capacity on TCH, reaching 322.58 mg/g. Acid-base titration, XRD, TEM, SEM, BET, and FI-TR analyses indicate that LDO has more active sites on the surface, the “memory effect”, and a larger specific surface area. In contrast, the removal rate of OFX by LDO is low because OFX has a more stable quinolone ring structure. Furthermore, after five adsorption-desorption cycles, the adsorption rate of TCH remains at 94.9%, demonstrating that LDO has good cyclic adsorption capacity for TCH. This study creatively combines acid-base buffering characteristics to study the mechanism of the adsorption of antibiotics by hydrotalcite, and proposes that LDO can be used as a special adsorbent for TCH.