Organic electronics have gained widespread attention due to their flexibility, lightness, and low-cost potential. It is attractive due to the possibility of large-scale roll-to-roll processing. However, organic electronics require additional development before they can be made commercially available and fully integrated into everyday life. To achieve feasibility for commercial use, these devices must be biocompatible and flexible while maintaining high performance. In this study, biocompatible silk fibroin (SF) was integrated with a mesh of silver nanowires (AgNWs) to build up flexible organic solar cells with maximum power conversion efficiency of up to 6.62%. The AgNW/SF substrate exhibits a conductivity of ∼11.0 Ω/sq and transmittance of ∼80% in the visible light range. These substrates retained their conductivity, even after being bent and unbent 200 times; this surprising ability was attributed to its embedded structure and the properties of the specific SF materials used. To contrast, indium tin oxide on synthetic plastic substrate lost its conductivity after the much less rigid bending. These lightweight and silk-based organic solar cells pave the way for future biocompatible interfaces between wearable electronics and human skin.