Novel biomaterials for bio‐ and chemical sensing applications have gained considerable traction in the diagnostic community with rising trends of using biocompatible and lowly cytotoxic material. Hydrogel‐based electrochemical sensors have become a promising candidate for their swellable, nano‐/microporous, and aqueous 3D structures capable of immobilizing catalytic enzymes, electroactive species, whole cells, and complex tissue models, while maintaining tunable mechanical properties in wearable and implantable applications. With advances in highly controllable fabrication and processability of these novel biomaterials, the possibility of bio‐nanocomposite hydrogel‐based electrochemical sensing presents a paradigm shift in the development of biocompatible, “smart,” and sensitive health monitoring point‐of‐care devices. Here, recent advances in electrochemical hydrogels for the detection of biomarkers in vitro, in situ, and in vivo are briefly reviewed to demonstrate their applicability in ideal conditions, in complex cellular environments, and in live animal models, respectively, to provide a comprehensive assessment of whether these biomaterials are ready for point‐of‐care translation and biointegration. Sensors based on conductive and nonconductive polymers are presented, with highlights of nano‐/microstructured electrodes that provide enhanced sensitivity and selectivity in biocompatible matrices. An outlook on current challenges that shall be addressed for the realization of truly continuous real‐time sensing platforms is also presented.