This two-part volume LNCS 16305 and 16306 constitutes the proceedings of the 21st IFIP International Conference on Network and Parallel Computing, NPC 2025, which was held in Nha Trang, Vietnam, during November 14-16, 2025.The 76 full papers included in this volume were carefully reviewed and selected from 223 submissions. Topics of interest include, but are not limited to, parallel and distributed applications and algorithms, parallel and distributed architectures and systems, and parallel and distributed software environments and tools.