Al-doped ZnO nanostructures were prepared via a simple precipitation method and were characterized by several techniques including XRD, TEM, EDX, UV–Vis, and DLS. All XRD patterns show the hexagonal single-phase structure of pure and Al-doped ZnO nanopowders without impurity. The samples consist of particles with average sizes ranging from 53 to 60 nm measured by DLS technique. Next, the catalytic activity of pure and Al-doped ZnO nanopowders was investigated in terms of synthesis of 3,4,5-substituted furan-2(5H)-one derivatives using the three-component reaction of aldehydes, aromatic amines, and acetylenic esters. This procedure has advantages such as high yields, simple methodology, and easy work-up.