This review explores the potential of microRNAs (miRs) in treating intervertebral disc degeneration (IVDD), a common cause of low back pain. IVDD affects nearly 40% of adults and is characterized by the degeneration of the intervertebral disc (IVD), leading to symptoms such as pain and loss of disc height. The review highlights the dysregulation of multiple miRs in IVDD and their therapeutic potential when delivered via nanomedicines. **Key Points:** 1. **miR Biogenesis and Regulation:** MiRs are small non-coding RNAs that play crucial roles in regulating gene expression. They can modulate signaling pathways and influence cellular processes, making them potential therapeutic targets. 2. **Dysregulated miRs in IVDD:** Studies have identified several miRs that are upregulated or downregulated in IVDD, including miR-21, miR-25-3p, miR-129-5p, and miR-155. These miRs are involved in processes such as cell apoptosis, ECM degradation, and inflammation. 3. **Regulation by lncRNAs and circRNAs:** Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can regulate miR expression, contributing to the degenerative process in IVDD. For example, lncRNA-HOTAIR and circRNA-GRB10 have been shown to influence miR activity and contribute to the degenerative cycle. 4. **Extracellular Vesicles (EVs):** EVs, including exosomes and microvesicles, can carry miRs and other molecules, facilitating intercellular communication. EVs derived from bone marrow mesenchymal stromal cells (BMSCs) have shown therapeutic potential in IVDD models. 5. **Therapeutic Strategies:** The review discusses various strategies for delivering miRs to treat IVDD, including synthetic oligonucleotides (antagomirs, ASOs, LNAs), lncRNAs, and decoy vectors (miR sponges). These approaches aim to either inhibit upregulated miRs or restore downregulated miRs to their normal levels. 6. **Nanomedicine for Nucleic Acid Delivery:** Nanoparticles are effective carriers for delivering miRs due to their ability to protect miRs from degradation and enhance cellular uptake. Different types of nanoparticles, such as lipid-based and polymer-based nanoparticles, have been investigated for their potential in treating IVDD. The review emphasizes the need for innovative treatments for IVDD, highlighting the potential of miR-targeting nanomedicines as a promising approach. The successful delivery of nucleic acids using nanomedicine technology opens new avenues for treating IVDD by targeting the underlying molecular mechanisms.This review explores the potential of microRNAs (miRs) in treating intervertebral disc degeneration (IVDD), a common cause of low back pain. IVDD affects nearly 40% of adults and is characterized by the degeneration of the intervertebral disc (IVD), leading to symptoms such as pain and loss of disc height. The review highlights the dysregulation of multiple miRs in IVDD and their therapeutic potential when delivered via nanomedicines. **Key Points:** 1. **miR Biogenesis and Regulation:** MiRs are small non-coding RNAs that play crucial roles in regulating gene expression. They can modulate signaling pathways and influence cellular processes, making them potential therapeutic targets. 2. **Dysregulated miRs in IVDD:** Studies have identified several miRs that are upregulated or downregulated in IVDD, including miR-21, miR-25-3p, miR-129-5p, and miR-155. These miRs are involved in processes such as cell apoptosis, ECM degradation, and inflammation. 3. **Regulation by lncRNAs and circRNAs:** Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) can regulate miR expression, contributing to the degenerative process in IVDD. For example, lncRNA-HOTAIR and circRNA-GRB10 have been shown to influence miR activity and contribute to the degenerative cycle. 4. **Extracellular Vesicles (EVs):** EVs, including exosomes and microvesicles, can carry miRs and other molecules, facilitating intercellular communication. EVs derived from bone marrow mesenchymal stromal cells (BMSCs) have shown therapeutic potential in IVDD models. 5. **Therapeutic Strategies:** The review discusses various strategies for delivering miRs to treat IVDD, including synthetic oligonucleotides (antagomirs, ASOs, LNAs), lncRNAs, and decoy vectors (miR sponges). These approaches aim to either inhibit upregulated miRs or restore downregulated miRs to their normal levels. 6. **Nanomedicine for Nucleic Acid Delivery:** Nanoparticles are effective carriers for delivering miRs due to their ability to protect miRs from degradation and enhance cellular uptake. Different types of nanoparticles, such as lipid-based and polymer-based nanoparticles, have been investigated for their potential in treating IVDD. The review emphasizes the need for innovative treatments for IVDD, highlighting the potential of miR-targeting nanomedicines as a promising approach. The successful delivery of nucleic acids using nanomedicine technology opens new avenues for treating IVDD by targeting the underlying molecular mechanisms.