The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon (IFN) genes (cGAS-STING) signaling pathway is crucial for sensing abnormal DNA accumulation in the cytoplasm. Once binds to abnormal DNA, cGAS catalyzes the production of second messenger cyclic dinucleotides, followed by the activation of downstream STING. This activation induces the expression of type I interferon and other inflammatory cytokines, ultimately initiating an immune response. Due to the involvement of the cGAS-STING pathway in various diseases, including infection, tumor, autoimmune disease and kidney disease, ongoing research is focused on developing drugs and treatment methods to target and regulate this pathway. With the development of nanotechnology, nanomedicines targeting cGAS-STING signaling are of great significance in clinical applications due to their targeted delivery, controlled drug release, improved solubility, multifunctionality, and enhanced stability. This comprehensive review focuses on the most recent progress of nanoplatforms targeting cGAS-STING in disease therapy, aiming to provide references and guidelines for further design and optimization of nanomedicines.