In this work, the bioaccessibility of polymethoxyflavones (PMFs) loaded in high internal phase emulsions (HIPE, ϕoil = 0.82) stabilized by whey protein isolate (WPI)-low methoxy pectin (LMP) complexes was evaluated using in vitro lipolysis and dynamic in vitro intestinal digestion studies. PMFs loaded HIPE was prepared by using aqueous dispersion of pre-formed biopolymeric complexes (WPI-LMP, 2:1 ratio) as the external phase and medium chain triglycerides oil (containing PMFs extracted from citrus peel) as the dispersed phase. The in vitro lipolysis study revealed that PMFs in HIPE became bioaccessible much higher than PMFs in medium chain triacylglycerols oil (MCT oil). In addition, by simulating the entire human gastrointestinal (GI) tract, the GI model TIM-1 demonstrated a 5- and 2-fold increase in the total bioaccessibility for two major PMFs encapsulated in HIPE, i.e. tangeretin (TAN) and nobiletin (NOB), respectively, as opposed to PMFs in MCT oil. Together these results from the digestion study showed that the incorporation of a high amount of PMFs into the viscoelastic matrix of HIPE could represent an innovative and effective way to design an oral delivery system. Such a system could be used to control and to improve the delivery of lipophilic bioactive compounds within the different compartments of the digestive tract, especially the human upper GI tract.