This book constitutes the proceedings of the 21st International Conference on Practical Applications of Agents and Multi-Agent Systems, PAAMS 2023, held in Guimaraes, Portugal, in July 2023. The 32 full papers in this book were reviewed and selected from 70 submissions. 5 demonstration papers are also included in this volume. The papers deal with the application and validation of agent-based models, methods, and technologies in a number of key applications areas, including: advanced models and learning, agent-based programming, decision-making, education and social interactions, formal and theoretic models, health and safety, mobility and the city, swarms and task allocation.