We report drug nanocrystals stabilized with host-specific serum proteins with high loading (∼63% w/w). The human serum derived curcumin nanoparticles (Cur-NanoSera) showed superior in vitro anticancer efficiency compared to a free drug with substantial hemocompatibility. The preadsorbed protein coating impeded further protein corona formation, even with repeated serum exposures. Acute and subacute toxicity evaluations post single and dual injections of C57BL/6 mice indicated that Cur-NanoSera showed no prominent inflammatory response or organ damage in the in-bred mice. Passive accumulation of Cur-NanoSera in tumor tissue significantly suppressed its growth in a syngeneic breast tumor model in addition to controlling tumor burden associated splenomegaly.