Various nanotechnologies have been extensively developed to prepare nanoparticles with different features for satisfying the requirements of diverse fields, but the current achievements are confined to different material systems for the limited acquisition with desirable properties. Here, we demonstrated a flexible strategy based on the broad selectivity of amines in the condensation of green tea polyphenol-EGCG (epigallocatechin gallate), formaldehyde, and amines for the rational design and preparation of versatile nanomaterials. With EGCG as the sole material system and amines (R–NH2) of various functional R groups as the selectable modules, the modular assembly of polyphenol-activated condensation was straightforward and completed in one step, giving rise to different polyphenolic nanoparticles variable in surface chemistry (−amine, −aldehyde, and −carboxyl), shapes (sphere, dumbbell, walnut), internal structures (solid, hollow, and porous), stimuli responsiveness (-s-s-), and fluorescence. The flexibility of the polyphenolic condensation for versatile nanoparticles was further demonstrated by the incorporation of amino-containing anticancer or antibacterial drugs into polyphenolic nanoparticles as nanodrugs. The present study totally involved the use of 13 different amines to synthesize 18 different nanoparticles, not only convincingly specifying the enormous value of the polyphenolic condensation as platform for modular assembly of versatile nanoparticles but also revolutionizing the current strategies and methodologies for encapsulated applications of tea polyphenols.