This study aimed at developing protein nanoparticles with desirable loading efficiency (LE) and low cross-linker concentration. Using β-lactoglobulin (BLG) and curcumin as a model system, this work demonstrated that the LE could be improved by up to 157% by maintaining low antisolvent content before mild evaporation. Moreover, the optimal level of glutaraldehyde decreased by 50% as the curcumin/protein ratio increased, suggesting that toxic cross-linkers could be partly replaced with natural phenols such as curcumin. The BLG-curcumin nanoparticles showed average size of 164-214 nm, zeta potential of -42 mV, and LE of up to 11%. Interestingly, BLG nanoparticles demonstrated rapid disintegration and nutraceutical release in simulated gastric fluid (SGF) at pH 2, despite the known resistance of BLG against pepsin. However, they maintained integrity in SGF at pH 5. This phenomenon, followed by extensive degradation in simulated intestinal fluid, suggested the controlled-release property of BLG nanoparticles when administered orally.