Piperine-loaded mesoporous silica nanoparticles (MSNPs) were synthesized by chemical methods from tetraethylorthosilicate (TEOS) as a precursor, N-cetyl trimethyl ammonium bromide (CTAB) as a surfactant, piperine, distilled water, and sodium hydroxide (NaOH) as a catalyst at 80°C. After stirring the mixture for 20-30 min, the synthesized combined substances were washed with ethanol and the surfactant was removed using hydrochloric acid (HCl). The morphological characterization was assessed by high-resolution-transmission electron microscope (HR-TEM), scanning electron microscopy (field emission [FE]-scanning electron microscopy [SEM]), FE-SEM-energy-dispersive x-ray (EDX), infrared Fourier transform infrared spectroscopic (FTIR), x-ray diffractometer (XRD), dynamic light scattering (DLS), and ultraviolet-visible (UV-VIS). HR-TEM final report showed the amorphous nature of the prepared nanoparticles (NPs). TEM image at 100 nm showed typical ball-like geometry with an average particle size of 13.05 nm. FE-SEM analysis proved that MSNPs loaded with piperine have a spherical shape with various nm ranges starting from 232 to 552 nm. The results of the piperine release test observed 93.70% of the drug (piperine) over 24 h. The in vivo toxicity analysis of piperine-loaded MSNPs tested using adult zebrafish showed no toxic effect. Our developed piperine-loaded MSNPs are favorable for achieving sustained release, a lower dose frequency, and better therapeutic effects.