Triptolide has proven to possess anticancer potential and been widely used for anti-cancer research. However, the liver and kidney toxicity has limited its application in cancer treatment. In this study, a drug delivery system based on mPEG-DPPE/calcium phosphate was developed to co-load triptolide and curcumin (TP and Curc-NPs). The coefficient of drug interaction (CDI) was calculated to determine the optimal concentration of the two drugs. When the concentration of triptolide was 25.22 ng/mL and the concentration of curcumin was 6.62 μg/mL, the two drugs reached the maximum synergistic killing effects on SKOV-3 tumor cells. The TP and Curc-NPs was prepared using ultrasonic emulsification. Flow cytometry results revealed that the TP and Curc-NPs arrested cell-cycle in the S and G2/M phases and exhibited a strong ability to induce apoptosis. Intracellular reactive oxygen species (ROS) results indicated that curcumin could reduce the intracellular ROS level caused by triptolide. The mRNA levels of heat shock protein (HSP) were detected by qTR-PCR and the results showed that the TP and Curc-NPs could lower the HSP70 mRNA level while could not reduce the HSP90 mRNA level. The animal experiments demonstrated the favorable curative effects of the TP and Curc-NPs, and the tumor inhibition rate reached 68.78%. The results of the pathological examinations demonstrated that the nanoparticles had no significant toxic effects on important organs. In conclusion, the TP and Curc-NPs exerted synergistic effects on ovarian cancer in vitro and in vivo, and the toxicity caused by triptolide may be reduced by curcumin through anti-oxidative stress effects. The TP and Curc-NPs could be a promising strategy for ovarian cancer.