Graphene-based two-dimensional (2D) materials act as a pivotal role in the area of advanced health, however, there are still some challenges such as controllable formulation and health risks of graphene, and green sustainability assessment of graphene. There is an emerging trend to develop a sustainable graphene-based 2D nanomaterials with biocompatibility, acceptable cytotoxicity, excellent anticoagulant properties, which are capability of accomplishing in vitro and in vivo assays, drug loading, antimicrobials, photochemical therapies, gene therapies, and bio-imaging. This comprehensive review article provides a thoroughly and real-time overview of the main aspects concerning graphene-based 2D nanomaterials and their applications in life and health. Our focus is on the potential risks and hazards of graphene-based 2D materials to the human body, especially in the biological roles of cell membranes, DNA, proteins, enzymes, cells and tissues and organs. In addition, functionalized modifications of graphene-based 2D materials are briefly outlined, and current restrictions and future orientations are considered. In a broader perspective, graphene denotes a conceptually sustainable 2D nanomaterial class and provides a new access point to health and will continue to offer a new horizon of opportunities for its next-generation applications.