Abstract In recent years there has been a spur of interest in the utilization of nano and micro-particles to fabricate novel food-grade Pickering emulsions. Aligned with increased interest and efforts to promote health through food, this study aimed to extend the understanding of Pickering emulsions stabilized by lactoferrin (LF) nano-particles in respect to their stability and responsiveness to physiological conditions of the human mouth and stomach. Analytical centrifugation revealed that LF nano-particles did not alter mean droplet size of coarse emulsions but significantly (p < 0.05) reduced creaming rates by an order of magnitude. In fine emulsions produced through high pressure homogenization, the use of nano-particles increased mean droplet sizes. This resulted in noted (p < 0.05) differences in stability with emulsions stabilized by LF nano-particles and alginate showing poorest stability. Concomitantly, the use of i-carrageenan and LF nano-particles yielded emulsions with the most reduced creaming (<1 μm/s), even compared to emulsions stabilized by native LF. Interestingly, the use of alginate and i-carrageenan with LF nano-particles also altered emulsion stability to artificial saliva and modulated emulsion behavior under gastric conditions, which was linked to reduced rate of LF gastric proteolysis. Overall, this work establishes a new possibility to incorporate LF in emulsions and demonstrates how LF nano-particles could be harnessed to modulate emulsion destabilization and breakdown in the mouth and stomach.