IoT devices are typically resource-constrained, with limited computational power, storage, and energy. Holochain, an emerging distributed ledger technology (DLT), offers the benefits of blockchain while overcoming its limitations, such as the reliance on consensus algorithms and a globally synchronized ledger. As a result, Holochain has garnered attention in the research community as a promising solution for distributed IoT applications. This paper reviews various DLTs in IoT distributed networks, focusing on the motivation for utilizing Holochain in these environments. We explore its key applications, challenges, and research insights. We propose the HoloSec framework, a conceptual security framework for IoT distributed networks that leverages Holochain’s agent-centric architecture, advanced cryptography, and machine learning (ML). The paper also illustrates the setup and implementation of a Holochain-based IoT network for a healthcare scenario and compares the performance of Holochain with traditional blockchain solutions. Initial experimental results show that Holochain achieves a latency of around 50 ms for data publishing and 30 ms for retrieval, with a throughput of approximately 20 transactions per second (TPS) on a single node, significantly outperforming blockchain, which shows higher latency (200 ms publish, 100 ms retrieve) and lower throughput (10 TPS). Finally, we examine key challenges associated with Holochain and outline future research directions aimed at enhancing its interoperability, scalability, security, and regulatory compliance in IoT environments.