Abstarct: Understanding the adsorption-desorption behavior of organic contaminants such as antibiotics on clay minerals may play an important role in controlling the fate and transport of these compounds in the environment. This study aimed to investigate Vancomycin (VAN) adsorption from aqueous solutions by raw bentonite nanoparticles (R-B) and bentonite nanoparticles modified with manganese oxide (Mn-B) and to evaluate desorption of VAN from the adsorbents. Adsorbent characterization was investigated using SEM, XRD, BET, EDX and FTIR analyses. The effect of various parameters such as adsorbent dosage, pH, contact time, initial concentration and ionic strength on the adsorption and desorption processes were also studied. The results showed that adsorption of VAN onto R-B strongly depends on pH and ionic strength in contrast to modified adsorbent. The presence of C-O-C and C=C groups in FTIR results, confirmed the VAN adsorption by the adsorbents. The results indicated that the adsorption processes for both adsorbents followed pseudo second order and Langmuir models. The maximum adsorption capacity for R-B and Mn-B was 370.37 and 322.58 mg.g-1, respectively. pH and ionic strength had a slight effect on VAN sorption on Mn-B. These findings demonstrate the advantage of modified bentonite in comparison to raw bentonite. Investigation of VAN desorption from adsorbents exhibited that the amount of desorbed VAN increases with increasing the cation (Na+, Ca2+ and Al3+) concentrations and desorption process is totally pH-dependent. Moreover, desorption power at the high initial loadings in the presence of salts follows the order of AlCl3 > CaCl2 > NaCl. This phenomenon is suggesting that cations with higher positive charges, or in other words, smaller hydrated ions are preferred to remove adsorbed VAN. Generally, the results revealed that cation exchange is the main mechanism for VAN sorption and desorption by the adsorbents.