Metal-organic frameworks (MOFs) offered excellent catalytic activity due to their superior porosity, and high densities of catalytic sites in remarkable specific surfaces. In this research, we prepared a magnetic nanocomposite based on MOF-5 which is one of the prominent and practical structures that have been reported in many applications, and investigated the advantages of it as a catalyst. The multi-functional catalyst was prepared in five steps including (1) preparation of cobalt ferrite nanoparticles (CoFe₂O₄), (2) surface modification of cobalt ferrite using tetraethyl orthosilicate, (3) surface functionalization using 3-aminopropyl triethoxysilane, (4) preparation of MOF-5, (5) preparation of CoFe₂O₄@SiO₂–NH₂@MOF-5 nanocomposite. The resulting catalyst was evaluated by FTIR, FESEM, EDX, XRD, and VSM analyses. The CoFe₂O₄@SiO₂–NH₂@MOF-5 nanocomposite was applied as a catalyst for the quinazoline derivatives’ synthesis. Various products were prepared with significant yields (90–98%) in short reaction times (20–60 min) without difficult work-up. In addition, the magnetic behavior of the catalyst allows it to be collected and recycled by a magnet and applied for six consecutive cycles without significantly reducing its efficiency. Quinazoline derivatives showed significant biological activities so their antioxidant activity was between 23.7% and 88.9% and their antimicrobial activity was in contradiction of E. coli, S. enterica, L. monocytogenes, S. aureus, and E. faecalis.