To systematically study the multiple effects of nanoparticles (NPs) on the stability, interfacial activity, and digestive properties of Pickering emulsions (PEs), various oil-in-water PEs were prepared by NPs based on the self-assembled α-lactalbumin-derived peptides with a variety of morphologies, stiffnesses, and sizes. We discovered that PEs stabilized by small-sized and soft nanospheres (NSs) exhibited the highest stability compared with other nanoparticles observed by Turbiscan during storage. Dilational interfacial rheological analysis demonstrated that a highly elastic interfacial film of the NSs had been formed by orderly packing at oil/water interfaces. Meanwhile, the most stable Pickering emulsion stabilized by NSs possessed the lowest lipid digestion rate. The tubular NPs distributed unevenly at the oil-water interfaces therefore showed lower interfacial activity. Harder NPs with lower flexibility showed a lower emulsion stability. Curcumin was loaded in PEs to further study the effect of bioavailability. Moreover, in vivo pharmacokinetic results revealed that Pickering emulsion stabilized by NSs showed the highest curcumin bioavailability, which was 5.37 times higher than unencapsulated curcumin. This study suggested that Pickering emulsion stabilized by NSs with the optimum stability was the most promising delivery system for hydrophobic bioactive ingredients.