Distributed quantum information processing is essential for building quantum networks and enabling more extensive quantum computations. In this regime, several spatially separated parties share a multipartite quantum system, and the most natural set of operations are Local Operations and Classical Communication (LOCC). As a pivotal part in quantum information theory and practice, LOCC has led to many vital protocols such as quantum teleportation. However, designing practical LOCC protocols is challenging due to LOCC’s intractable structure and limitations set by near-term quantum devices. Here we introduce LOCCNet, a machine learning framework facilitating protocol design and optimization for distributed quantum information processing tasks. As applications, we explore various quantum information tasks such as entanglement distillation, quantum state discrimination, and quantum channel simulation. We discover novel protocols with evident improvements, in particular, for entanglement distillation with quantum states of interest in quantum information. Our approach opens up new opportunities for exploring entanglement and its applications with machine learning, which will potentially sharpen our understanding of the power and limitations of LOCC.