Implantable electronics can be used to continuously monitor and modulate electrophysiological signals. However, the mechanical mismatch between conventional rigid electronic components and soft biological tissue can lead to tissue damage and inflammation, whereas the elastomers typically used to create soft electronics can also have low biocompatibility. Here we report an elastomeric organic field-effect transistor that is made from a blend of semiconducting nanofibres and a biocompatible elastomer. The composite film, which is specifically based on poly[(dithiophene)-alt-(2,5-bis(2-octyldodecyl)-3,6-bis(thienyl)-diketopyrrolopyrrole)] and bromo isobutyl–isoprene rubber, exhibits high mechanical stretchability and biocompatibility with a similar Young’s modulus to human tissues and stable electrical performance under 50% strain. In addition, the integration of a biocompatible dual-layer silver and gold metallization results in robust, stretchable and biofluid-corrosion-resistant electrodes. Our biocompatible and stretchable transistors exhibit stable operation in logic circuits (including inverters, NOR gates and NAND gates) under physiological conditions. In vitro assessments with human dermal fibroblasts and macrophages show no adverse effects on cell viability, proliferation or migration. We also examine the long-term integration potential of the transistors via in vivo implantation studies in mice, which show no major inflammatory response or tissue damage. Biocompatible and stretchy organic field-effect transistors can be created using a vulcanized blend film of semiconducting nanofibres and a medical-grade elastomer.