Polypeptoids represent a significant class of synthetic analogues of natural polypeptides with potential biomimetic applications in materials, catalysis, and pharmaceuticals, but their simple and general synthesis still remains a key challenge. Herein, we demonstrate that Ugi reaction of natural amino acids leads to structurally diverse polypeptoids, including γ- and δ-, as well as poly(ε-peptoid)s, under mild conditions (open to air, room temperature, and catalyst free).