Lung cancer accounts for 11.4% of all cancer cases and 1.8 million deaths annually, yet therapy resistance and high mortality persist as critical clinical challenges. Manju Bargavi Sakthivel and colleagues from the Meenakshi Academy of Higher Education and Research reviewed the adjuvant potential of berberine—a bioactive compound with a 3,000-year medicinal history—to optimize management strategies for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Therefore, the comprehensive synthesis evaluates in vitro lung cancer cell lines, such as A549 and H1299, alongside animal xenografts to determine berberine's impact on tumor progression. • Gene Regulation: Data demonstrates that berberine impairs the genomic integrity of cancer cells by downregulating genes essential for deoxyribonucleic acid (DNA) replication and repair. Berberine’s role in enhancing lung cancer treatment: Exploring mechanisms, efficacy, and adjuvant potential.