This study aimed to synthesize and characterize chitosan-coated noisomal doxorubicin for the purpose of enhancing its medical application, particularly in the field of cancer treatment. Doxorubicin, a potent chemotherapeutic agent, was encapsulated within noisomes, which are lipid-based nanocarriers known for their ability to efficiently deliver drugs to target sites. Chitosan, a biocompatible and biodegradable polysaccharide, was used to coat the surface of the noisomes to improve their stability and enhance drug release properties. The synthesized chitosan-coated noisomal doxorubicin was subjected to various characterization techniques to evaluate its physicochemical properties. Transmission electron microscopy (TEM) revealed a spherical structure with a diameter of 500–550 ± 5.45 nm and zeta potential of +11 ± 0.13 mV with no aggregation or agglomeration. Chitosan-coated noisomes can loaded doxorubicin with entrapping efficacy 75.19 ± 1.45%. While scanning electron microscopy (SEM) revealed well-defined pores within a fibrous surface. It is observed that chitosan-coated niosomes loading doxorubicin have optimum roughness (22.88 ± 0.71 nm). UV spectroscopy was employed to assess the drug encapsulation efficiency and release profile. Differential scanning calorimetry (DSC) helped determine the thermal behavior, which indicated a broad endotherm peak at 52.4 °C, while X-ray diffraction (XRD) analysis provided information about the crystallinity of the formulation with an intense peak at 23.79°. Fourier-transform infrared spectroscopy (FTIR) indicated the formation of new bonds between the drug and the polymer. The findings from this study will contribute to the knowledge of the physical and chemical properties of the synthesized formulation, which is crucial for ensuring its stability, drug release kinetics, and biological activity. The enhanced chitosan-coated noisomal doxorubicin has the potential to improve the effectiveness and safety of doxorubicin in cancer treatment, offering a promising strategy for enhanced medical applications.