The use of live biological substrates in the fabrication of unconventional computing (UC) devices is steadily transcending the barriers between science fiction and reality, but efforts in this direction are impeded by ethical considerations, the field’s restrictively broad multidisciplinarity and our incomplete knowledge of fundamental biological processes. As such, very few functional prototypes of biological UC devices have been produced to date. This thesis aims to demonstrate the computational polymorphism and polyfunctionality of a chosen biological substrate — slime mould Physarum polycephalum, an arguably ‘simple’ single-celled organism — and how these properties can be harnessed to create laboratory experimental prototypes of functionally-useful biological UC prototypes. Computing devices utilising live slime mould as their key constituent element can be developed into a) heterotic, or hybrid devices, which are based on electrical recognition of slime mould behaviour via machine-organism interfaces, b) whole-organism-scale morphological processors, whose output is the organism’s morphological adaptation to environmental stimuli (input) and c) intracellular processors wherein data are represented by energetic signalling events mediated by the cytoskeleton, a nano-scale protein network. It is demonstrated that each category of device is capable of implementing logic and furthermore, specific applications for each class may be engineered, such as image processing applications for morphological processors and biosensors in the case of heterotic devices. The results presented are supported by a range of computer modelling experiments using cellular automata and multi-agent modelling. We conclude that P. polycephalum is a polymorphic UC substrate insofar as it can process multimodal sensory input and polyfunctional in its demonstrable ability to undertake a variety of computing problems. Furthermore, our results are highly applicable to the study of other living UC substrates and will inform future work in UC, biosensing, and biomedicine.