In this work, a one-pot multicomponent synthesis of the ibuprofen-loaded Fe3O4 nanoparticles-supported zeolitic imidazolate framework-8 (Ibu-ZIF-8/Fe3O4 NPs) nanohybrid was carried out. The ZIF-8/Fe3O4 NPs nanohybrid was used as a drug carrier for the in vitro release of ibuprofen in a PBS solution. The structure and morphology of the synthesized materials were investigated by powder X-ray diffraction (PXRD) analysis, transmission electron microscopy (TEM) analysis, UV-visible absorption studies, FTIR spectroscopy, and thermogravimetric analysis (TGA). The ibuprofen release kinetics was studied by UV-visible spectroscopy. The mechanism of drug delivery was thoroughly investigated and the Higuchi model was found as the best-fitted model for the ibuprofen release study. The 20 wt % Fe3O4 NPs-supported ZIF-8 nanohybrid exhibited more than 95% ibuprofen release efficiency in phosphate buffer saline of pH 7.4 within 2 h. The separation ability of the nanohybrid was very good, and it was easily separated by a simple commercial magnet. In order to investigate the cell viability, the cytotoxicity of ZIF-8, Fe3O4 NPs, and ZIF-8/20 wt % Fe3O4 NPs was investigated using MTT assays against Leishmania donovani promastigotes. The ZIF-8/20 wt % Fe3O4 NPs nanohybrid carrier exhibited a cell growth inhibition effect with a high correlation coefficient and low probability (p) values. The high release of drug molecules may be due to the more open site of the ZIF-8/Fe3O4 NPs nanohybrid. The drug release profile suggests that the nanohybrid can be potentially used as a drug carrier for targeted drug delivery systems.