Drugs treatment including antibiotics or herbal medicines cannot cure osteomyelitis effectively accompanied by drug‐resistance bacteria and even amputation after long‐term debridement. Herein, a materioherbological strategy is utilized to construct a smart nanovector of cationic starch (CS) modified curcumin nanoparticles (CS@Cur NPs) for treating methicillin‐resistant Staphylococcus aureus (MRSA) induced osteomyelitis. On the one hand, CS modification can reduce the π–π accumulation of curcumin to endow the nanocomposite with excellent water solubility. On the other hand, the hydroxyl group in the curcumin is hydrogen‐bonded to the carbonyl group in the monomer (methyl methacrylate, MMA) of CS, resulting in a decrease in both the bandgap (between the highest and lowest occupied molecular orbitals, labeled as ΔE) and the S1–T1 energy gap (ΔES‐T) while the spin–orbital coupling (SOC) values increase, which benefits the formation of triplet‐state molecules under ultrasonic irradiation, significantly improving the yields of reactive oxygen species (ROS) capacity. The CS@Cur NPs nanocomposite constructed in this paper produced a large number of ROS synergic targeting effects under continuous 15 min ultrasonic irradiation, the clearance rate of MRSA infection induced osteomyelitis in rats can be as high as 99.93%. This study provides a new therapeutic strategy for the treatment of osteomyelitis induced by pathogenic bacteria.