The peripheral nervous system (PNS) regulates the exchange of sensory information and motor commands between the body and the central nervous system. Further, through the autonomic nervous system, the PNS plays a pivotal role in controlling vital physiological processes. For treating various PNS-related and non-neurological conditions, neurotechnologies interfacing with the PNS are critical. Yet, precisely stimulating or inhibiting target fibers remains a significant challenge due to the complex morphology and composition of nerves. Traditional peripheral nerve interfaces, relying on electrical stimulation, grapple with a problematic tradeoff between selectivity and invasiveness. Extraneural cuff electrodes are considered the safest yet least selective. Cuffs present other issues too, like lead migration, fracture, infection, and nerve injury, often due to inadequate sizing and use of rigid/compressive materials. This thesis introduces an approach to tackle these obstacles through the development of a soft peripheral nerve interface. The system's translational potential was experimentally validated in small and large animal models. Moreover, the interface was designed to incorporate optical stimulation functionality, allowing for advanced selective stimulation strategies. The first part of the work centers on the development of a soft, adaptable cuff electrode. Using a 150 µm silicone layer (E~1 MPa) as the base material, and incorporating stretchable thin-film gold tracks, the cuff was designed to adapt to a range of nerve sizes and shapes. It features a unique belt-like structure, ensuring near-complete perimeter coverage and facilitating implantation. Electrochemical characterization and rat sciatic nerve testing confirmed the device's stable performance across varying conditions. The cuff's applicability was further demonstrated in translational applications involving pig sciatic nerve stimulation and vagus nerve recording. The 16-channel stimulating cuff demonstrated the ability to selectively activate up to five muscles, with comparable and improved performances to existing systems. Additionally, integration of rigid light sources within a soft cuff for opto-modulation was explored. Despite initial challenges related to strain gradients in soft-rigid systems, the developed cuff maintained conformability and LED functionality while stretching (~ 35% strain). As a proof-of-concept, spatially distinct stimulation of sciatic nerve from four separate sites was demonstrated, indicating potential for high-density, stretchable optoelectronic interfaces. Lastly, nerve-on-a-chip systems were leveraged ex vivo to explore novel peripheral neuromodulation strategies. These platforms, which amplify and track propagating action potentials from explanted nerve rootlets, hold great promise for elucidating the complex mechanisms behind ultrasonic and optical stimulation techniques, and for optimizing strategies before in vivo validation. In conclusion, this work contributes to simplifying the implantation procedure of cuffs, enabling intimate contact with varying nerve sizes, achieving remarkable selectivity even in complex fascicular organization and providing an improved chronic (6-week) biointegration. Furthermore, the integration of optical stimulation and the development of ex vivo testing strategies propels the optimization and characterization of novel modulation methods, thus enhancing our understanding of peripheral neural mechanisms.