MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are increasingly being explored as targets for anticancer drug development. The first miRNA-based drug, MRX34, a miR-34 mimic delivered via liposomes, entered phase I clinical trials for advanced hepatocellular carcinoma in 2013. miRNAs, typically 19–24 nucleotides long, are processed from primary transcripts by Drosha and Dicer, and regulate gene expression by binding to the 3′-UTR of target mRNAs. However, recent studies reveal that miRNAs can also regulate gene expression through other mechanisms, such as enhancing translation or affecting protein synthesis. LncRNAs are also involved in cancer and other diseases, highlighting the importance of non-coding RNAs in cancer biology. miRNAs play diverse roles in cancer development and progression. For example, miR-15a/16-1 acts as a tumor suppressor by targeting anti-apoptotic proteins, while miR-21 is oncogenic and promotes cancer progression. miRNAs can also influence tumor metastasis by regulating genes involved in cell migration and invasion. Additionally, miRNAs can be secreted as exosomes, acting as hormones to influence distant cells. miRNAs are also involved in epigenetic regulation, affecting gene expression through interactions with DNA methyltransferases. The development of miRNA therapeutics involves strategies to restore or block miRNA function. miRNA mimics, which are synthetic miRNA oligonucleotides, can be used to restore tumor suppressor miRNAs, while anti-miRs inhibit oncogenic miRNAs. Small molecules targeting miRNAs (SMIRs) are also being explored, though their specificity and mechanism of action are not fully understood. Challenges in miRNA therapy include off-target effects, the need for efficient delivery systems, and the complexity of assessing therapeutic efficacy. Combination therapies using miRNAs and chemotherapeutic agents show promise in enhancing treatment outcomes. For example, miR-128b restoration may reverse glucocorticoid resistance in leukemia, while miR-30c can sensitize cancer cells to chemotherapy. Overall, miRNAs and lncRNAs represent promising targets for cancer therapy, with ongoing research aimed at developing effective and safe therapeutic strategies.MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are increasingly being explored as targets for anticancer drug development. The first miRNA-based drug, MRX34, a miR-34 mimic delivered via liposomes, entered phase I clinical trials for advanced hepatocellular carcinoma in 2013. miRNAs, typically 19–24 nucleotides long, are processed from primary transcripts by Drosha and Dicer, and regulate gene expression by binding to the 3′-UTR of target mRNAs. However, recent studies reveal that miRNAs can also regulate gene expression through other mechanisms, such as enhancing translation or affecting protein synthesis. LncRNAs are also involved in cancer and other diseases, highlighting the importance of non-coding RNAs in cancer biology. miRNAs play diverse roles in cancer development and progression. For example, miR-15a/16-1 acts as a tumor suppressor by targeting anti-apoptotic proteins, while miR-21 is oncogenic and promotes cancer progression. miRNAs can also influence tumor metastasis by regulating genes involved in cell migration and invasion. Additionally, miRNAs can be secreted as exosomes, acting as hormones to influence distant cells. miRNAs are also involved in epigenetic regulation, affecting gene expression through interactions with DNA methyltransferases. The development of miRNA therapeutics involves strategies to restore or block miRNA function. miRNA mimics, which are synthetic miRNA oligonucleotides, can be used to restore tumor suppressor miRNAs, while anti-miRs inhibit oncogenic miRNAs. Small molecules targeting miRNAs (SMIRs) are also being explored, though their specificity and mechanism of action are not fully understood. Challenges in miRNA therapy include off-target effects, the need for efficient delivery systems, and the complexity of assessing therapeutic efficacy. Combination therapies using miRNAs and chemotherapeutic agents show promise in enhancing treatment outcomes. For example, miR-128b restoration may reverse glucocorticoid resistance in leukemia, while miR-30c can sensitize cancer cells to chemotherapy. Overall, miRNAs and lncRNAs represent promising targets for cancer therapy, with ongoing research aimed at developing effective and safe therapeutic strategies.