MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration (IVDD) are emerging as promising therapeutic strategies. IVDD is a major cause of low back pain, affecting nearly 80% of adults, with 40% attributed to degeneration of the intervertebral disc (IVD). Current treatments are limited to symptomatic relief, necessitating innovative approaches. MicroRNAs (miRs) are dysregulated in IVDD and play critical roles in cellular processes, making them potential therapeutic targets. However, miR delivery faces biological barriers, which can be overcome by encapsulating miRs in nanoparticles, enhancing their stability and cellular uptake. miRs are small non-coding RNAs that regulate gene expression by modulating signaling pathways. They are involved in various aspects of IVDD, including cell apoptosis, ECM degradation, and inflammation. miR dysregulation is associated with the progression of IVDD, and several miRs, such as miR-21, miR-25-3p, miR-129-5p, and miR-155, have been identified as key players. These miRs can be targeted using inhibitors or delivered as mimics to restore their function. Additionally, non-coding RNAs like lncRNAs and circRNAs regulate miR activity, offering new avenues for therapeutic intervention. Nanomedicine has advanced significantly, with nanoparticles serving as effective carriers for miR delivery. The use of extracellular vesicles (EVs) for miR delivery is gaining traction, as EVs can transport miRs to target cells. Studies have shown that miR-loaded EVs can mitigate IVDD by reducing ECM degradation and inflammation. The development of stimuli-responsive nanomedicines further enhances the potential of miR-based therapies. In summary, miR-targeting nanomedicines offer a promising approach for treating IVDD by targeting the underlying molecular mechanisms. These therapies involve either inhibiting dysregulated miRs or delivering miR mimics to restore their function. The use of nanoparticles and EVs enhances the delivery and efficacy of miR-based treatments, making them a viable option for the management of IVDD. Further research is needed to optimize these strategies and translate them into clinical applications.MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration (IVDD) are emerging as promising therapeutic strategies. IVDD is a major cause of low back pain, affecting nearly 80% of adults, with 40% attributed to degeneration of the intervertebral disc (IVD). Current treatments are limited to symptomatic relief, necessitating innovative approaches. MicroRNAs (miRs) are dysregulated in IVDD and play critical roles in cellular processes, making them potential therapeutic targets. However, miR delivery faces biological barriers, which can be overcome by encapsulating miRs in nanoparticles, enhancing their stability and cellular uptake. miRs are small non-coding RNAs that regulate gene expression by modulating signaling pathways. They are involved in various aspects of IVDD, including cell apoptosis, ECM degradation, and inflammation. miR dysregulation is associated with the progression of IVDD, and several miRs, such as miR-21, miR-25-3p, miR-129-5p, and miR-155, have been identified as key players. These miRs can be targeted using inhibitors or delivered as mimics to restore their function. Additionally, non-coding RNAs like lncRNAs and circRNAs regulate miR activity, offering new avenues for therapeutic intervention. Nanomedicine has advanced significantly, with nanoparticles serving as effective carriers for miR delivery. The use of extracellular vesicles (EVs) for miR delivery is gaining traction, as EVs can transport miRs to target cells. Studies have shown that miR-loaded EVs can mitigate IVDD by reducing ECM degradation and inflammation. The development of stimuli-responsive nanomedicines further enhances the potential of miR-based therapies. In summary, miR-targeting nanomedicines offer a promising approach for treating IVDD by targeting the underlying molecular mechanisms. These therapies involve either inhibiting dysregulated miRs or delivering miR mimics to restore their function. The use of nanoparticles and EVs enhances the delivery and efficacy of miR-based treatments, making them a viable option for the management of IVDD. Further research is needed to optimize these strategies and translate them into clinical applications.