We present a novel type of all-aqueous nonionic layer-by-layer films of silk fibroin with synthetic macromolecules and a natural polyphenol. We found the multilayer growth and stability to be strongly pH-dependent. Silk assembled with poly(methacrylic) and tannic acids at pH = 3.5 disintegrated at pH ∼ 5, while silk/poly(N-vinylcaprolactam) interactions were stable at low and high pH values but resulted in thinner films at a high pH. The results suggest that the intermolecular interactions are primarily driven by hydrogen bonding with a considerable contribution of hydrophobic forces. We also demonstrated that cubical, spherical, and platelet capsules with silk-containing walls can be constructed using particulate sacrificial templates. This work sets a foundation for future explorations of natural and synthetic macromolecules assemblies as biomimetic materials with tunable properties. © 2012 American Chemical Society.