Colorectal cancer (CRC) is a leading cause of death worldwide due to its aggressive nature and drug resistance, which limit traditional treatment effectiveness. Recent studies highlight the role of microRNAs (miRNAs) in tumorigenesis, metastasis, and chemotherapy resistance, with miRNA-155 emerging as a key player in CRC. miRNA-155 exerts dual effects, inducing drug resistance while serving as a potential therapeutic target. It regulates a wide array of mRNA transcripts associated with apoptosis, cell cycle regulation, and DNA repair, impacting various cellular pathways. Overexpression of miRNA-155 is linked to resistance against multiple chemotherapeutic drugs, promoting tumor cell survival, proliferation, and the epithelial-mesenchymal transition (EMT) process by repressing tumor suppressors and activating oncogenes. Additionally, miRNA-155 holds promise as a diagnostic and prognostic marker due to its association with CRC patient survival rates. However, its regulatory mechanisms across CRC subtypes remain unclear. This study provides insights into miRNA-155's role in CRC, focusing on its involvement in therapeutic resistance and potential as a therapeutic target. We also explore its significance as a prognostic biomarker and emphasize its therapeutic applications based on evidence from human, in vivo, in vitro, and clinical studies.