<p indent="0mm">Persistent organic pollutants (POPs) have been widely concerned due to their bioaccumulation, environmental persistence, and strong toxic effects on humans and organisms. Oral digestion via food, dust, and soil is the most important route for humans to uptake POPs. However, not all POPs that enter human body are bioavailable, thus exposure risk assessment based on the total amount of POPs in matrices would overestimate the resulting health risks. Measurement of bioaccessibility using <italic>in vitro</italic> gastrointestinal (GI) digestive simulation has been used to predict the bioavailability of POPs. In this paper, the impacts of <italic>in vitro</italic> experimental approaches, properties of oral matrices, compositions of digestive fluid, and properties of POPs on the bioaccessibility of POPs in oral exposure matrices are comprehensively reviewed and analyzed. The dynamic <italic>in vitro</italic> GI digestive simulation improved the accuracy of the results compared with traditional static GI digestive simulation. The digestion of nutrients in the GI tract and cooking methods affect the distribution of POPs between matrices and digestive fluids, thus affecting bioaccessibility. Lipids generally enhanced the bioaccessibility of most POPs because they promote the formation of stable fatty acid-bile salt micelles and increase the solubility of POPs in digestive fluid. However, this solubilization effect of mixed micelles does not apply to POPs with very high hydrophobicity because they prefer to distribute in the undigested food matrix. The bioaccessibility of POPs is mostly positively correlated with the carbohydrate content of food, whereas the effects of protein and dietary fiber were uncertain. Particle size and organic matter content of dust or soil are important factors affecting the bioaccessibility of POPs. The smaller the particle size of the dust or soil, the larger specific surface area, and the digestive fluid displayed strong capacity to dissolve POPs, thus increasing their bioaccessibility. Organic matter has a significant effect on the adsorption and desorption of POPs from dust or soil. The higher the organic matter content, the more POPs will be adsorbed, thus hindering the release of POPs from the matrices. Bile salts and various digestive enzymes such as pepsin and trypsin can also change the bioaccessibility of POPs by affecting the digestion process of matrices. There is generally a negative relationship between the bioaccessibility of POPs and their log<italic>K</italic><sub>OW</sub> values. The higher the hydrophobicity of POPs, the more difficult it is to dissolve in the digestive fluid. Different migration routes of POPs will also lead to different bioaccessibility, and the bioaccessibility of POPs adsorbed into the matrices is higher than that of POPs existing as a component of matrices. When considering bioaccessibility, the estimated daily intake of POPs from a matrix will decrease and the estimated exposure risk will therefore be reduced. Thus the contribution of POPs via different matrices to total human exposure should be re-examined. Collectively, bioaccessibility should be fully considered in the assessment of oral exposure and health risk to ensure accurate results. There are still some limitations in the current research. Firstly, results obtained using different <italic>in vitro</italic> methods varied widely and validation with <italic>in vivo</italic> data is lacking. Secondly, current studies mostly focused on only one oral matrix which cannot represent rich daily diets and different exposure scenarios among different populations. Thirdly, there is still a big gap in the research on the bioaccessibility of emerging POPs and the mixed exposure to multiple POPs. This paper provides an important theoretical basis for the accurate assessment of the human exposure risk of POPs, and for formulating measures to reduce the oral exposure risk of POPs in different populations.