In this study, platinum nanoparticles (PtNPs) were synthesized and their potential to improve the efficacy of doxorubicin (DOX) in cancer treatment was investigated. H2PtCl6, LiAlH4, and trisodium citrate were used during the synthesis of PtNPs. They were characterized using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and scanning transmission electron microscopy (STEM). The diameter of the PtNPs was measured to be 21.72 nm without DOX loading and approximately 212 nm after DOX loading (DOX-PtNPs). FTIR confirmed the binding of DOX to PtNPs. In addition, MTT assays showed that DOX-PtNPs have a stronger effect on MCF-7 and HCT116 cancer cells than free DOX, even at low doses. The IC value for MCF-7 cells treated with DOX was determined to be 4.81 µg/ml, while it was significantly lower for the DOX-PtNP group at 0.64 µg/ml. A similar trend was observed in HCT116 cells, where the IC value for DOX was 5.03 µg/ml, while for DOX-PtNPs it was 0.62 µg/ml. In summary, the activity of DOX in these cells was increased approximately eightfold by PtNPs. Moreover, DOX-PtNPs showed no significant cytotoxic effects on normal HUVEC cells at low doses. Moreover, DOX-PtNPs enhanced apoptotic activity in HCT116 cells without inducing drug resistance as demonstrated by Rho123 staining and annexin/PI analyses. The significance of this study lies in the pioneering use of DOX-PtNPs in colon cancer, the synthesis of smaller PtNPs, the eightfold increase in the efficacy of DOX, and the demonstration that DOX-PtNPs do not significantly increase drug resistance.