This chapter has provided an overview of modified chitosan nanoparticles for the chemotherapy. In this connection, the review about doxorubicin hydrochloride (Dox-HCl) has been reported as an antibiotic which is used to treat cancer in general. In order to address the issues of the localized chemotherapy, collagen/chitosan film containing biofinylated glycol CSNPs have been reported. Localized chemotherapy is often used to boost the immune system and stop the growth of secondary tumors. It may prevent side effects and provide medications at a physical location for an extended length of time. Doxorubicin-loaded polyethylene glycoylated and poloxemer-modified CSNPs have also been reported which claim to increase the drug exposure. Magnetic nanoparticles (MNPs) have gained popularity in chemotherapy in recent years due to their ability to target tumor cells in a magnetic field. Paclitaxel is a chemotherapic medication that belongs to the alkaloid family used for the cancer treatment. Vincristine is another anticancer alkaloid that is used to treat a variety of cancers with chitosan-loaded nanoparticles. Methotrexate has been reported as a chemotherapeutic drug that has been used to treat lung cancer, breast cancer, choriocarcinoma, leukemia, and trophoblastic tumors, among other malignancies. Apart from various chitosan-based medicines, the chapter has also provided an overview about the applications of modified CSNPs for localized chemotherapy such as for cervical cancer treatment. Cervical cancer is the second most frequent disease in women in the world, and it is the leading cause of cancer death in developing countries. Curcumin-loaded CSNPs have been found to boost anticervical cancer inflammatory activity. The chitosan nanoparticles have also been analyzed for the brain and breast cancer treatment.