Advanced organic bioelectronics enable smooth fusion between modern electronics and biological systems for better physiological monitoring and pathological examinations. Photon‐regulated bioelectronics are especially desirable due to the non‐contact impact, remote‐control, and even self‐powered operation. However, few studies have addressed the advanced photon‐enabled organic photoelectrochemical transistor (OPECT) biosensors capable of operation at zero gate bias. Here, on the basis of a hydrogel/graphene oxide hybrid (denoted as HGH), a multifunctional HGH‐gated OPECT biosensor is presented, which is exemplified by Ca2+‐triggered gelation on the CdS quantum dot (QD) photoelectrode linking with a sandwich immunoassay toward human IgG as the model target. Gelation of HGH on the CdS QD gate electrode can not only inhibit the interfacial mass transfer on the gate/electrolyte interface, but also significantly block the light absorption of CdS QDs, leading to the corresponding change of the channel currents of OPECT device. At zero gate bias, this OPECT biosensor exhibits high gain in response to light and good analytical performance for human IgG with a detection limit of 50 fg mL–1. Given the numerous intelligent hydrogel materials and their potential interactions with light, this work unveils a general platform for developing a new class of hydrogel‐gated OPECT bioelectronics and beyond. A multifunctional hydrogel‐gated organic photoelectrochemical transistor biosensor is constructed using a Ca2+‐triggered hydrogel/graphene oxide hybrid on the CdS quantum dot photosensitive gate electrode linking with a sandwich immunoassay toward human IgG as the model target. The proposed biosensor exhibits high gain in response to light and good analytical performance at zero gate bias.