Controlling Biomedical Functionality through Stereochemistry: A Foundation for Precision Diagnostics and Therapeutics ^†

Comprehensive Summary As a fundamental feature of physiological regulation in living systems, chirality has emerged as a critical factor in the rapid development of nanomaterials for biomedical applications. Through precise structural design, chiral nanomaterials enable high‐precision biological analysis and efficient therapeutic interventions by exploiting handedness‐dependent interactions at chiral organic–inorganic hybrid interfaces or through chiral light–matter coupling. This review systematically outlines synthetic strategies for diverse chiral nanomaterials, spanning three primary material categories: inorganic ( e.g. , chiral metal nanoparticles, nanographenes, carbon nanotubes, mesoporous silica nanoparticles, and quantum dots), organic ( e.g. , chiral covalent organic frameworks and DNA nanomaterials), and organic–inorganic hybrid systems ( e.g. , chiral metal nanoclusters and metal−organic frameworks). For each category, we undertake a comprehensive discussion of established methodologies for imparting or controlling chirality, including direct synthesis, post‐synthetic modification, and template‐guided assembly, among others. Furthermore, we summarize the applications of these chiral nanomaterials across several frontier biomedical domains, including biosensing, antitumor therapy, antibacterial treatment, as well as tissue engineering and regeneration. Particularly, the focus is on elucidating how nanoscale chirality influences fundamental biological processes, including molecular signaling, cellular uptake, proliferation, and immune responses in order to establish structure‐activity relationships that link the design of chiral nanomaterials with their macroscopic biological functions. Finally, we examine the key challenges impeding clinical translation, including the unclear mechanisms governing the interactions of chiral nanomaterials with biological systems, the paucity of diverse functional chiral ligands, and unresolved issues concerning long‐term biosafety. We also offer perspectives on future directions for chiral nanomaterials, including AI‐driven design and advanced biorelevant testing platforms to study systematic structure–activity relationships, thereby accelerating the development of enantioselective nanomedicine. This work aims to provide theoretical guidance for the rational design of chiral nanomaterials with tailored biological functionalities, thereby advancing solutions to pressing challenges in life sciences. Key Scientists