Antimicrobial peptides (AMPs), particularly buforins, show significant anticancer potential. Buforins, derived from histone H2A, exhibit antibacterial and anticancer activities. Buforin IIb and its analogs demonstrate selectivity for cancer cells, inducing apoptosis and inhibiting tumor growth in various cancers, including HeLa, breast, lung, ovarian, prostate, and liver cancers. Buforins interact with cancer cell surface receptors, inhibit cell proliferation, and disrupt mitochondrial functions, leading to cell death. They also target phosphatidylserine on cancer cells, enhancing selectivity. Buforins can be conjugated with nanoparticles or liposomes to improve stability, bioavailability, and targeted delivery. These bioconjugates enhance therapeutic efficacy by reducing off-target effects and overcoming drug resistance. Despite challenges like low stability and bioavailability, buforins and their derivatives represent a promising approach for targeted cancer therapy. Further research and clinical trials are needed to fully evaluate their potential in cancer treatment.Antimicrobial peptides (AMPs), particularly buforins, show significant anticancer potential. Buforins, derived from histone H2A, exhibit antibacterial and anticancer activities. Buforin IIb and its analogs demonstrate selectivity for cancer cells, inducing apoptosis and inhibiting tumor growth in various cancers, including HeLa, breast, lung, ovarian, prostate, and liver cancers. Buforins interact with cancer cell surface receptors, inhibit cell proliferation, and disrupt mitochondrial functions, leading to cell death. They also target phosphatidylserine on cancer cells, enhancing selectivity. Buforins can be conjugated with nanoparticles or liposomes to improve stability, bioavailability, and targeted delivery. These bioconjugates enhance therapeutic efficacy by reducing off-target effects and overcoming drug resistance. Despite challenges like low stability and bioavailability, buforins and their derivatives represent a promising approach for targeted cancer therapy. Further research and clinical trials are needed to fully evaluate their potential in cancer treatment.