This book constitutes the refereed proceedings of the 15th International Conference on Unconventional Computation and Natural Computation, UCNC 2016, held in Manchester, UK, in July 2016. The 15 revised full papers presented together with 5 invited papers were carefully reviewed and selected from 30 submissions. The papers cover a wide range of topics including molecular, cellular, quantum, optical and chaos computing; cellular automata; neural and evolutionary computation; artificial immune systems; Ant algorithms and swarm intelligence; amorphous computing; membrane computing; computational systems biology and computational neuroscience; and synthetic biology. .