The interaction between drug carrier and drug molecules is fundamental for the study of drug delivery, drug targeting, and drug release. Until now, little has been known about the interaction at the molecular level. X-Ray absorption near edge structure (XANES) spectroscopy is a sensitive tool for identifying this interaction. Herein, we report the use of calcium and silicon K-edge X-ray absorption near edge structure (XANES) spectroscopy to investigate how drug molecules interact with different functional groups in calcium silicate hydrate and anhydrous calcium silicate nanocarriers with different morphologies. Significant changes are observed in the XANES spectra after drug loading; ibuprofen (IBU) loading leads to the ordering of silicates locally and there is loss of hydrates during the IBU loading processes.