Optoelectronic biointerfaces have made a significant impact on modern science and technology from understanding the mechanisms of the neurotransmission to the recovery of the vision for blinds. They are based on the cell interfaces made of organic or inorganic materials such as silicon, graphene, oxides, quantum dots, and 𝝅-conjugated polymers, which are dry and stiff unlike a cell/tissue environment. On the other side, wet and soft hydrogels have recently been started to attract significant attention for bioelectronics because of its high-level tissue-matching biomechanics and biocompatibility. However, it is challenging to obtain optimal opto-bioelectronic devices by using hydrogels requiring device, heterojunction, and hydrogel engineering. Here, an optoelectronic biointerface integrated with a poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate), PEDOT:PSS, hydrogel that simultaneously achieves efficient, flexible, stable, biocompatible, and safe photostimulation of cells is demonstrated. Besides their interfacial tissue-like biomechanics, ≈34 kPa, and high-level biocompatibility, hydrogel-integration facilitates increase in charge injection amounts sevenfolds with an improved responsivity of 156 mA W −1 , stability under mechanical bending , and functional lifetime over three years. Finally, these devices enable stimulation of individual hippocampal neurons and photocontrol of beating frequency of cardiac myocytes via safe charge-balanced capacitive currents. Therefore, hydrogel-enabled optoelectronic biointerfaces hold great promise for next-generation wireless neural and cardiac implants.