In this research, a natural bioactive glabridin (Glab) flavonoid compound was encapsulated in zeolitic imidazolate framework-8 (ZIF-8) via one-pot technique at room temperature. Herein, ~98.7% of drug was encapsulated into ZIF-8 coreshell, which depicted 28.44% drug encapsulation productivity of ZIF-8. Fourier transform infrared (FTIR), UV‒Vis spectroscopy and X‑ray crystallography (XRD) confirmed the drug encapsulation. Next, the newly constructed nanomaterials were greatly studied with, dynamic light scattering (DLS), scanning electron microscope (SEM), energy-dispersive X-ray (EDX) analysis, transmission electron microscope (TEM) and thermo gravimetric analysis (TGA) technologies. SEM and TEM showed hexagonal morphology of Glab@ZIF-8 and an increased particle size to that of ZIF-8 i.e., 138.62±5.4 nm and 91.69±6.2 nm, respectively. TGA depicted 32.14% Glab@ZIF-8 material’s decomposition at 644 °C. The antibacterial efficacy of Glab@ZIF-8 was found superior against S. aureus than E. coli and Bacillus subtilis, resulting 26±0.01 mm, 23±0.02 mm and 11±0.01 mm inhibition zones and MIC values 31.2 µg, 62.5 µg and 125 µg, separately. Though, the Glab@ZIF-8 kept in an acidic medium (pH 5) for 72 h showed highest drug release 89.76% as compared to the pH 5.5 (81.23%) and pH 7.4 (24.78%). In conclusion, ZIF-8 remained a potential drug delivery system and Glab@ZIF-8 nanocomposite can be accredited for broader biomedical applications to cure infection diseases and malignant cells.