Two-dimensional (2D) nanomaterials (e.g., graphene) have attracted growing attention in the (bio)sensing area and, in particular, for biomedical applications because of their unique mechanical and physicochemical properties, such as their high thermal and electrical conductivity, biocompatibility, and large surface area. Graphene (G) and its derivatives represent the most common 2D nanomaterials applied to electrochemical (bio)sensors for healthcare applications. This review will pay particular attention to other 2D nanomaterials, such as transition metal dichalcogenides (TMDs), metal–organic frameworks (MOFs), covalent organic frameworks (COFs), and MXenes, applied to the electrochemical biomedical (bio)sensing area, considering the literature of the last five years (2018–2022). An overview of 2D nanostructures focusing on the synthetic approach, the integration with electrodic materials, including other nanomaterials, and with different biorecognition elements such as antibodies, nucleic acids, enzymes, and aptamers, will be provided. Next, significant examples of applications in the clinical field will be reported and discussed together with the role of nanomaterials, the type of (bio)sensor, and the adopted electrochemical technique. Finally, challenges related to future developments of these nanomaterials to design portable sensing systems will be shortly discussed.