This book constitutes the proceedings of the 12th International Conference on Biomimetic and Biohybrid Systems, Living Machines 2022, in Genoa, Italy, held in July 19–22, 2022. The 44 full papers and 14 short papers presented were carefully reviewed and selected from 67 submissions. They deal with research on novel life-like technologies inspired by the scientific investigation of biological systems, biomimetics, and research that seeks to interface biological and artificial systems to create biohybrid systems. The conference aims to highlight the most exciting research in both fields united by the theme of “Living Machines.”