The growing crisis of antibiotic resistance calls for advanced and sustainable antibacterial strategies. In the past few years, lanthanide‐doped upconversion nanoparticles (UCNPs) with unique photophysical properties have been innovatively explored for bacterial detection and therapy, and hold promise for alleviating challenges faced in the post‐antibiotic era. In this review, the interface engineering for the bacteria‐targeted UCNP nanoplatforms is highlighted, the principles and merits of various upconversion detection strategies are discussed, and the latest progress in UCNP‐based antibacterial applications are summarized, especially in deep‐tissue infection imaging and therapy. Finally, the remaining concerns and future efforts for practical applications are put forward. This review is expected to provide comprehensive guidance for diagnosing and combating bacterial infections based on advanced UCNP nanoplatforms.

The rapid emergence of drug‐resistant bacteria has raised a great social concern together with the impetus for exploring advanced antibacterial ways. NIR‐triggered antimicrobial photodynamic therapy (PDT) by lanthanide‐doped upconversion nanoparticles (UCNP) as energy donor exhibits the advantages of high tissue penetration, broad antibacterial spectrum and less acquired resistance, but is still limited by its low efficacy. Now we designed a bio‐inorganic nanohybrid and combined lysozyme (LYZ) with UCNP‐PDT system to enhance the efficiency against resistant bacteria. Benefiting from the rapid adhesion to bacteria, intelligently bacteria‐responsive LYZ release and synergistic LYZ‐PDT effect, the nanoplatform achieves an exceptionally strong bactericidal capacity and conspicuous bacteriostasis on methicillin‐resistant S. aureus. These findings pave the way for designing efficiently antibacterial nanomaterials and provide a new strategy for combating deep‐tissue bacterial infection.