Purpose <p>Cancer remains a leading cause of mortality worldwide, with traditional chemotherapy frequently limited by issues such as drug resistance, modest efficacy, and severe side effects. This review explores the potential of anticancer peptides (ACPs) as a novel and promising therapeutic strategy that targets cancer cells through unique mechanisms designed to reduce the likelihood of resistance.</p> Methods <p>The review conducts an in-depth examination of current literature on ACPs, focusing on their classification, structural diversity, and mechanisms of action. It emphasizes the role of chemical modifications—such as substituting neutral or anionic residues with cationic amino acids and introducing specific chemical groups—to enhance membrane-disruptive potency. Additionally, it evaluates the impact of computational techniques, including high-throughput screening and structural optimization, on accelerating ACP development.</p> Results <p>Findings indicate that ACPs, due to their flexible and customizable structures, can specifically target cancer cells while sparing normal cells through membrane disruption. The ability to fine-tune these peptides enhances their potency and selectivity, making them promising candidates for therapeutic medicines and vaccines. The incorporation of advanced computational approaches has significantly streamlined the discovery and optimization process, contributing to several candidates currently undergoing rigorous clinical trials.</p> Conclusion <p>ACPs provide an effective alternative to conventional chemotherapy by tackling significant issues such as drug resistance and detrimental side effects. The ongoing breakthroughs in chemical modification approaches and computational approaches continue to enable these peptides to transform cancer therapy, facilitating more effective and tailored therapeutic alternatives in oncology.</p>