Abstract Pumice-derived silica aerogel (PDSA) was successfully synthesized as an efficient adsorbent for ibuprofen removal. A multilayer of highly stable and high density amine groups was successfully grafted on the PDSA surface using a nonpolar solvent and tetraethyl orthosilicate as a co-hydrolyzer, at 80 °C, under reflux. The amine grafted pumice-derived silica aerogel (AMPDSA) was utilized for efficient removal of ibuprofen. The characterization study by FTIR, XRD, FESEM, and TEM showed that the prepared AMPDSA had excellent adsorption activity and ability. The morphology of AMPDSA is characterized as amorphous phases, homogeneous, spherical particles containing silica, with a particle size of less than 25 nm and 407 m2/g specific surface areas and a well-defined pearl-like morphology. The isothermal data were correlated with a number of two-and-three parameters theoretical models. The Khan equation was the best fit among them giving a maximum adsorption capacity of 39.95 mg/g. The optimization study using the central composite design methodology by invoking the values of the analysis of variance, multiple R2, adjusted R2, and the Durbin–Watson statistic has ascertained a good fit between the adsorption data and the second order polynomial equation. This methodology predicted 100% removal of ibuprofen at conditions of contact time 150 min, 0.5 g/L of AMPDSA dose, 6.53 mg/L of initial ibuprofen concentration and pH close to 7. The results show that hydrophobic interactions, electrostatic and non-electrostatic interactions, such as hydrogen bonding control ibuprofen adsorption mechanism. Through the obtained results, the prepared AMPDSA can be used as an inexpensive and highly efficient adsorbent in the field of removal and remediation of pharmaceutical compounds.