The interactions between food macromolecules, particularly carbohydrates and fiber, with polyphenols are of significant relevance in elucidating the bioaccessibility of bioactive compounds in plants. White mugwort ( Artemisia lactiflora Wall., BK No.070334), a medicinal plant unique to Thailand, is a promising antioxidant for food fortification due to its phenolic acids (5-CQA, 3-CQA, 3,5-diCQA) and flavonoids (quercetin, kaemferol, morin, rutin, isovitexin). This study employed the Infogest static model for in-vitro digestion to examine the bio-accessibility of these compounds with carbohydrates (brown rice flour) and fiber (inulin). When the white mugwort extract powder (WME) was digested with these food macronutrients, structural modifications and hydrolysis occurred, resulting in reduced polyphenol bio-accessibility, particularly during the intestinal phase due to alkaline conditions. Moreover, WME was found to be delayed the brown rice starch digestion due to the ability to inhibit pancreatic amylase activity through non-covalent interaction. This reaction is formed between hydroxyl groups of phenolic and polar groups of enzymes. Moreover, inulin was detected to show the negative impact on bio-accessible polyphenols more than brown rice flour which could be due to the higher dietary fiber content of inulin over brown rice flour and the stronger binding capacity of polyphenols-dietary fiber. These reversible non-covalent interactions can be further metabolized by gut microorganisms before polyphenols are metabolized and reabsorbed in the large intestine. These findings suggest that consuming plant extract with other food macromolecules is not preferable to adding high concentrations of fiber powder. Naturally occurring plant fiber at lower levels does not significantly affect polyphenol bio-accessibility