The effects of in vitro digestion, hydrothermal treatment, and food matrices (wheat flour, durum wheat flour, wholemeal wheat flour, corn flour, rice flour) on the bioaccessibility of phenolic compounds (gallic acid, p-coumaric acid, ferulic acid, chlorogenic acid, catechin) were investigated. The influence of experimental factors and their combinations was estimated based on the “Dose Correction Index” (DCI) concept. Generally, the applied conditions had a negative effect on the bioaccessibility of polyphenols; however, the effect depended on the type of compound and food matrix, which was reflected in different DCI values. A less unfavorable effect on the bioaccessibility was exerted by the rice flour (the lowest DCI values), but the most negative impact was found in the case of the wholemeal wheat flour. The DCI concept provides basic knowledge of the magnitude of factors affecting the bioaccessibility of polyphenols, which can be useful for designing fortified products with desirable bioactivity.