Hydroxychloroquine is an immunomodulatory drug that has been used for 60 years to treat malaria and autoimmune diseases. On the other hand, metoclopramide belongs to a group of antiemetics, medicines used to prevent vomiting and treat its consequences. Once this pharmaceuticals present in manure, they may interact with different soil components or may be washed off into surface water or leached to ground water. Therefore, to prevent water contamination it is necessary to understand the mechanisms by which pharmaceuticals are retained and released from soil. In this study, the mechanism of desorption of hydroxychloroquine and metoclopramide from natural soils samples from Croatia is examined. Kinetics of desorption, the impact of ionic strength and the influence of pH on their`s desorption are studied. In order to determine the desorption mechanisms of hydroxychloroquine, Freundlich and Temkin isotherm model are applied by which certain parameters of desorption are determined. The obtained distribution coefficient, Kd, for tested soils is in range of 3909.4 mL/g to 7122.1 mL/g. Desorption of metoclopramide is shown by Freundlich and Dubinin-Radushkevich isotherms. For five soil samples, distribution coefficient is ranged from 27.299 mL/g to 594.63 mL/g. The rate of desorption is the best described with the kinetic model of pseudo-second order. Investigating the influence of ionic strength and pH, the results show that the values of sorption coefficient decreased with the increase in ionic strength of CaCl2 solution as well with its pH value.