Plant polyphenols are linked to health benefits, but their bioactivity depends on intestinal absorption, which is influenced by physicochemical properties and interactions with co-occurring compounds (1). While the absorption of individual polyphenols has been extensively studied, polyphenol–polyphenol interactions in complex plant extracts remain poorly understood. This study investigated these interactions using moringa extracts and Caco-2 cell monolayers to model the human intestinal epithelium. Extracts with varying polyphenol compositions were prepared using ultrasound-assisted extraction with methanol, ethanol, and acetone at different solvent–water ratios. Intestinal transport of 10 polyphenols was assessed by measuring apparent permeability coefficients (Papp) using liquid chromatography mass spectrometry (2). Regression modelling showed that the permeability of gallic acid, syringic acid, sinapic acid, caffeic acid, catechin, epicatechin, and quercetin was significantly influenced by co-occurring polyphenol concentrations, with strong predictive models (10-fold R² ≥ 70%). Permeability was generally low (Papp ≈ 0.1–5 × 10⁻⁶ cm/s; <10% transported), with more lipophilic compounds exhibiting higher permeability. A moderate positive correlation between initial concentration and transport rate (r = 0.69, p < 0.001) indicates that higher initial apical concentrations generally increase the rate of compound transport across the Caco-2 monolayer. Similarly, a strong positive relationship was observed between Papp and % transported (r = 0.98, p < 0.001), indicating that compounds with higher permeability exhibit greater translocation across the intestinal barrier. Cellular antioxidant activity varied among extracts but showed no clear relationship with permeability. These findings demonstrate that intestinal transport is strongly influenced by mixture composition and cannot be fully predicted from physicochemical properties alone, providing a framework for predicting polyphenol bioavailability in complex plant mixtures. This work highlights the importance of considering polyphenol mixtures rather than individual compounds when evaluating bioavailability and functional effects. This work provides a foundation for future studies to improve predictions of polyphenol absorption and cellular activity and to guide the design of functional foods and nutraceutical formulations.