Organic-inorganic hybrid nanoflowers (NF) with sizes or features on a nanoscale are a class of flower-shaped nanomaterials self-assembled from metal ions and organic components. Here, to be more specific, the organic components mainly refer to biomolecules ranging from proteins, peptides, and amino acids to DNA/RNA. Beyond their pleasing aesthetics, their unique properties and integrated functions have attracted widespread interest and made them promising candidates in the application of biomedical areas. Great efforts have been made to design and synthesize versatile functional hybrid nanoflowers. In this review, we begin with the clarification of versatile recently reported hybrid nanoflowers according to the types of metal ions and biomolecules employed. To highlight the design of organic-inorganic hybrid nanoflowers, their synthetic methods and mechanisms, structural and biological characteristics are discussed. After that, the state-of-the-art applications of hybrid nanoflowers in biomedical fields including biosensing, biocatalysis, and cancer therapy are demonstrated. In the end, we discuss the prospects of organic-inorganic hybrid nanoflowers and highlight the challenges and opportunities for future research.