The past decades have witnessed the rapid development in soft, stretchable, and biocompatible devices for applications in biomedical monitoring, personal healthcare, and human–machine interfaces. In particular, the design of soft devices in optics has attracted tremendous interests attributed to their distinct advantages such as inherent electrical safety, high stability in long-term operation, potential to be miniaturized, and free of electromagnetic interferences. As the alternatives to conventional rigid optical waveguides, considerable efforts have been made to develop light-guiding devices by using various transparent and elastic polymers, which offer desired physiomechanical properties and enable wearable/implantable applications in optical sensing, diagnostics, and therapy. Here, we review recent progress in soft and stretchable optical waveguides and sensors, including advanced structural design, fabrication strategies, and functionalities. Furthermore, the potential applications of those optical devices for various wearable and biomedical applications are discussed. It is expected that the newly emerged soft and stretchable optical technologies will provide a safe and reliable alternative to next-generation, smart wearables and healthcare devices.