Long non-coding RNAs, often referred to as lncRNAs, consist of RNA molecules that contain more than 200 nt and can be translated into small proteins under various circumstances. Extensive research has consistently demonstrated that long non-coding RNAs (lncRNAs) and miRNAs play a crucial role in various biological processes and disease mechanisms, including those associated with viral infections. Although numerous mechanisms are involved in miRNA and lncRNA-mediated gene regulation, such as transcriptional and translational regulation, protein modification, and the formation of RNA-protein complexes. This manuscript demonstrates the new therapeutic roles of long ncRNA (lncRNA) and microRNA (miRNA) in the treatment of HIV-1 infection. It shows that these non-coding RNAs have decisive roles in controlling the viral replication, latency, and host-virus interactions in the epigenetic, transcriptional and post-transcriptional processes. Select lncRNAs like MALAT1, NEAT1, NRON, and GAS5 are demonstrated to increase or block HIV transcription and persistence, whereas miRNAs like miRNA-155, miRNA-146a and miRNA-191- 5p regulate immune reactions and viral replication by acting on both viral RNA and host dynamics. The article also highlights that certain disadvantage of lncRNA such as delivery efficiency, stability of RNA therapeutics, potential off-target effects, and the difficulty of targeting HIV reservoirs.