Devices interfacing with biological tissues can provide valuable insights into function, disease, and metabolism through electrical and mechanical signals. However, certain neuromuscular tissues, like those in the gastrointestinal tract, undergo significant strains of up to 40%. Conventional inextensible devices cannot capture the dynamic responses in these tissues. This study introduces electrodes made from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and polydimethylsiloxane (PDMS) that enable simultaneous monitoring of electrical and mechanical responses of gut tissue. The soft PDMS layers conform to tissue surfaces during gastrointestinal movement. Dopants, including Capstone™ FS-30 and polyethylene glycol, are explored to enhance the conductivity, electrical sensitivity to strain, and stability of the PEDOT:PSS. The devices are fabricated using shadow masks and solution-processing techniques, providing a faster and simpler process than traditional clean-room based lithography. Tested on ex vivo mouse colon and human stomach, the device recorded voltage changes of up to 300 μV during contraction and distension consistent with muscle activity, while simultaneously recording resistance changes of up to 150% due to mechanical strain. These devices detect and respond to chemical stimulants and blockers, and can induce contractions through electrical stimulation. They hold great potential for studying and treating complex disorders like irritable bowel syndrome and gastroparesis. This article is protected by copyright. All rights reserved.