The polyphenolic compounds in fermented blueberry wine responsible for diarrhea induction were identified using a spectrum–effect relationship approach. Diarrhea-inducing effects of different doses of fermented blueberry wine were evaluated in mice. Eight types of macroporous adsorption resins were used to selectively remove polyphenols to varying extents, and changes in polyphenolic profiles were characterized using high-performance liquid chromatography coupled with diode array detection (HPLC–DAD). The effects of polyphenol depletion on diarrhea-related indicators were assessed, and spectrum–effect relationships were analyzed using grey relational analysis, orthogonal partial least squares analysis, and Spearman rank correlation analysis. The results showed that gavage administration of a threefold concentrated fermented blueberry wine at a dose of 30 μL.g-1 induced diarrhea in mice. A total of 50 polyphenolic compounds were identified, including 21 phenolic acids, 26 flavonoids, and 3 other polyphenols. Among the tested resins, NKA-II showed the highest adsorption efficiency, reducing the relative content of chlorogenic acid by 13.79%. After polyphenol removal, the diarrhea index decreased by 58.38%, intestinal propulsion was reduced by 32.74%, intestinal tissue damage was significantly alleviated, serum diamine oxidase activity decreased by 30.84%, and electrolyte imbalance was markedly improved (P<0.05). Spectrum–effect relationship analysis revealed a strong correlation between chlorogenic acid (P8) and diarrhea induction. Overall, chlorogenic acid was identified as the key polyphenolic compound responsible for diarrhea induction in fermented blueberry wine. These findings provide a scientific basis for quality control and safety evaluation of fermented blueberry wine.