Long non-coding RNA (LncRNA), with transcripts over 200 nucleotides in length, play critical roles in numerous biological functions and have emerged as significant players in the pathogenesis of osteoarthritis (OA), an inflammatory condition traditionally viewed as a degenerative joint disease. This review comprehensively examines the influence of LncRNA on the inflammatory processes driving OA progression, focusing on their role in regulating gene expression, cellular activities, and inflammatory pathways. Notably, LncRNAs such as MALAT1, H19, and HOTAIR are upregulated in OA and exacerbate the inflammatory milieu by modulating key signaling pathways like NF-κB, TGF-β/SMAD, and Wnt/β-catenin. Conversely, LncRNA like MEG3 and GAS5, which are downregulated in OA, show potential in dampening inflammatory responses and protecting against cartilage degradation by influencing miRNA interactions and cytokine production. By enhancing our understanding of LncRNA’ roles in OA inflammation, we can better leverage them as potential biomarkers for the disease and develop innovative therapeutic strategies for OA management. This paper aims to delineate the mechanisms by which LncRNA influence inflammatory responses in OA and propose them as novel targets for therapeutic intervention.