This volume, LNCS 16607, constitutes the thoroughly refereed prototypes and research-in-progress proceedings of the 21st International Conference on Design Science Research in Information Systems and Technology, DESRIST 2026, which was held in Münster, Germany, during June 8–10, 2026. Given the large number of high-quality contributions, the 2026 proceedings are published in three volumes: LNCS 16605 and 16606 as main proceedings include all accepted full papers, while LNCS 16607 contains of accepted Prototypes and Research-in-Progress Proceeding papers.DESRIST 2026 received a total of 231 submissions across all tracks and formats. The 23 research-in-progress papers and 14 prototype papers included in this volume were carefully reviewed and selected from 89 submissions across these two categories.The papers as Prototypes and Research-in-Progress Proceeding papers presented in LNCS 16607 are organized in the following topical sections:Design for Better Futures: Beyond the Science of the Artificial (Theme Track); “From Insight to Impact” (General Track); The Future of Financial Services; Future of Data-Driven and AI-Enabled Design; Future of Healthcare and Wellbeing; Future of Design and Entrepreneurship; Future of Responsible and Sustainable Design; Future of Design Science Education; Future of Design Science Methodology; Future of Ecosystems for Design Science Research; Prototypes Track.