Prostate cancer (PC) ranks among the most prevalent cancers in males. Recent studies have highlighted intricate connections between long non-coding RNAs (lncRNAs), natural products, and cellular signaling in PC development. LncRNAs, which are RNA transcripts without protein-coding function, influence cell growth, programmed cell death, metastasis, and resistance to treatments through pathways like PI3K/AKT, WNT/β-catenin, and androgen receptor signaling. Certain lncRNAs, including HOTAIR and PCA3, are associated with PC progression, with potential as diagnostic markers. Natural compounds, such as curcumin and resveratrol, demonstrate anticancer effects by targeting these pathways, reducing tumor growth, and modulating lncRNA expression. For instance, curcumin suppresses HOTAIR levels, hindering PC cell proliferation and invasion. The interaction between lncRNAs and natural compounds may open new avenues for therapy, as these substances can simultaneously impact multiple signaling pathways. These complex interactions offer promising directions for developing innovative PC treatments, enhancing diagnostics, and identifying new biomarkers for improved prevention and targeted therapy. This review aims to map the multifaceted relationship among natural products, lncRNAs, and signaling pathways in PC pathogenesis, focusing on key pathways such as AR, PI3K/AKT/mTOR, WNT/β-catenin, and MAPK, which are crucial in PC progression and therapy resistance. Regulation of these pathways by natural products and lncRNAs could lead to new insights into biomarker identification, preventive measures, and targeted PC therapies.