Colorectal cancer (CRC) is recognized as one of the most prevalent malignancies, both in terms of incidence and mortality rates. Current research into CRC has shed light on the molecular mechanisms driving its development. Several factors, including lifestyle, environmental influences, genetics, and diet, play significant roles in its pathogenesis. Natural compounds such as curcumin, tanshinone, lycorine, sinomenine, kaempferol, verbascoside, quercetin, berberine, and fisetin have shown great promise in the prevention and treatment of CRC. Research has also highlighted the significance of non-coding RNAs (ncRNAs) as biomarkers and therapeutic targets in CRC. Among these, long non-coding RNAs (lncRNAs) have been found to regulate the transcription of genes involved in cancer. LncRNAs contribute to cancer stem cell (CSC) proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and chemoresistance. Specific lncRNAs, including GAS5, LNC00337, HOTAIR, TPT1-AS1, cCSC1, BCAR4, TUG1, and Solh2, play crucial roles in these processes. They hold potential as novel biomarkers, detectable in bodily fluids and tissues, and could serve as therapeutic targets due to their involvement in drug resistance and sensitivity. These insights could improve CRC treatment strategies, addressing resistance to chemotherapy and radiotherapy. This review article aims to provide a comprehensive analysis of the current knowledge regarding the effectiveness of natural anti-cancer agents in CRC treatment. Additionally, it offers an in-depth evaluation of lncRNAs in CRC, their role in the disease's progression, and their potential applications in its management.