Aflatoxins (AFs) are difuranocoumarin derivatives produced as secondary metabolites by fungi belonging to several Aspergillus species. Aflatoxin B1 (AFB1) is one of the most potent naturally occurring hepatic carcinogens to both human and animals and is classified as a group (1) human carcinogen. Therefore, the aim of this study is to assess the effect of encapsulating polyvinylpyrrolidone (PVP 10, 360 and 1300 kDa)-Tannic acid complexed nanoparticles (PVP-TA NPs) inside yeast cell walls (YCW) to remediate AFB1 in the gastrointestinal models. Glucan Mannan Lipid Particles (GMLPs) from Saccharomyces cescerevisie cell walls showed the highest AFB1 adsorption in simulated gastric fluid (SGF) after 10 min, and in simulated intestinal fluid (SIF) after 1 h. Glucan Mannan Lipid Particles are hollow 3–4-micron porous microspheres that provide an efficient system for the synthesis and encapsulation of AFB1-absorbing nanoparticles (NPs). Although tannic acid (28%) was released from GMLP particles after three water washes, only 10, 5.6 and 7.6% of the total loaded TA was released when complexed with optimal ratios of PVP 10, 360 and 1300kDa; respectively. Fluorescence microscopic images supported the conclusion that PVP TA complexed NP cores were successfully synthesized inside the GMLPs. Encapsulation of PVP TA NPs inside GMLPs significantly increased the stability of the GMLP encapsulated PVP TA NPs formulation. Data also showed that AFB1 adsorption by the multi-functional GMLP PVP-TA NPs was enhanced synergistically in SGF and in SIF binding compared to individual GMLP.