<p>Utilizing DNA’s molecular programmability, massive parallelism, and minimal energy requirements, it emerges as a transformative medium for secure data storage and encryption. However, practical implementation is limited by technical challenges, particularly the development of robust, programmable systems for flexible data encoding, precise molecular operations, and reliable encryption. Here, we present a molecular information storage and encryption platform that integrates hierarchical core–shell DNA condensates with biomolecular computing networks. It allows programmable and rapid execution of core operations such as information encoding, erasure, rewriting, replication, and repair within readily accessible and readable DNA-based condensates. Moreover, programmable biomolecular computing circuits endowed the system with unprecedented encryption capabilities, including multi-level logic encryption, time-dependent dynamic encryption, living system-driven encryption and fine-grained access control of information. Together, this work represents a meaningful advancement in molecular information storage and encryption, with notable advantages in dynamic editability and system scalability.</p>