Silicon‐composed nanomedicines are one of the most representative inorganic nanosystems in theranostic biomedicine. The emerging of new family members of silicon‐composed nanosystems substantially contributes to their further clinical translation. 2D silicene/silicon nanosheets have recently been developed as an emerging topology of silicon‐composed nanoparticles, which features unique planar nanostructure with large surface area, abundant surface chemistry, specific physiochemical property, and desirable biological effects. This progress report highlights and discusses the state‐of‐art developments of the elaborate construction of 2D silicene/silicon nanosheets for versatile biomedical applications, including top–down fabrication, multifunctionalization, surface engineering, and their available biomedical applications in tumor theranostics (e.g., bioimaging, photothermal ablation, chemotherapy, chemoreactive nanotherapy, radiotherapy, and synergistic nanotherapy) and antibacteria. Their large surface area originating from 2D nanostructure not only enables efficient loading and delivery of chemotherapeutic drugs, but also guarantees the multifunctionalization. Especially, 2D silicene/silicon nanosheets harness desirable photothermal‐conversion performance for photonic hyperthermia and photoacoustic imaging in the near infrared biowindow, accompanied with the desirable biodegradability and biocompatibility, which is typically not possessed in other silicon‐composed counterparts. The multivariate analysis on the facing challenges and future developments of these 2D silicene/silicon nanosheets have also been conducted and outlooked for further underpinning their clinical translations.