Silk-based conductive materials are widely used in biointerface applications, such as artificial epidermal sensors, soft and implantable bioelectronics, and tissue/cell scaffolds. Such biointerface materials require coordinated physicochemical, biological, and mechanical properties to meet current practical needs and future sophisticated demands. However, it remains a challenge to formulate silk-based advanced materials with high electrical conductivity, good biocompatibility, mechanical robustness, and in some cases, tissue adhesion ability without compromising other physicochemical properties. In this review, we highlight recent progress in the development of functional conductive silk-based advanced materials with different morphologies. Then, we reviewed the advanced paradigms of these silk materials applied as wearable flexible sensors, implantable electronics, and tissue/cell engineering with perspectives on the application challenges. Silk-based conductive materials can serve as promising building blocks for biomedical devices in personalized healthcare and other fields of bioengineering.