Context: Vitamins have been shown to reduce chemotherapy-related fatigue (CRF) by conserving energy loss both during and after cancer treatment. However, it remains unknown whether this reduction of fatigue interferes with the cancer drugs or alters the effectiveness of these agents. Objectives: The objective was to synthesize vitamin-cisplatin-loaded chitosan nano-particles for chemoprevention and cancer fatigue. Materials and methods: Multi-vitamin (C, D3, and B12)-cisplatin composite nano-formulation called NanoCisVital (NCV) to overcome CRF. The interactions between vitamins and NCV were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, and a particle size analyser. The chemo-preventive activity was performed by in vitro bio assays. Results: SEM analysis showed spherical shape and the size is <225 nm. NCV inhibited the proliferating yeast cells as well as denaturation of bovine serum albumin, and it also reduced the sprouting of new blood vessels in dose-dependent manner. Conclusion: Collectively, these results demonstrate that the NCV particles can be used to reduce CRF without much affecting the anti-cancer properties of cisplatin.