Abstract: Pectin is a highly promising biosorbent for heavy metals; however, its adsorption performance for these metals during human digestion remains unclear. This study aimed to investigate the structural changes of citrus pectin with varying molecular weights during in vitro digestion and to evaluate its Pb²⁺ adsorption performance. Four citrus pectins (CP505, CP163, CP51, and CP21) with molecular weights of 505, 163, 51, and 21 kDa, respectively, were prepared using enzymatic hydrolysis combined with ultrafiltration. Their digestive behaviors were analyzed through an in vitro simulated digestion model, which included oral, gastric, and intestinal phases. Structural changes were characterized using Fourier-transform infrared spectroscopy (FTIR), high-performance size-exclusion chromatography coupled with multi-angle laser light scattering and refractive index detection (HPSEC-MALLS-RI), and dinitrosalicylic acid (DNS) assays. The Pb²⁺ adsorption capacity was determined through in vitro simulated adsorption experiments. The results indicated that, in comparison with the oral digestion phase, the molecular weight of pectin was significantly reduced during the intestinal digestion phase (e.g., a 35.20% decrease was observed for CP21), accompanied by an increase in reducing sugar content (a 40.06% rise for CP21) and a decrease in degree of esterification (a 59.22% reduction for CP21). Furthermore, the smaller the initial molecular weight of pectin, the more pronounced its degradation. In experiments involving Pb²⁺ adsorption, high-molecular-weight pectins (CP505 and CP163) achieved a removal rate of 38.03% for high-concentration Pb²⁺ (700 mg/L) during the oral phase. In the gastric phase, CP163 and CP51 demonstrated removal rates of 68.98% and 70.20%, respectively, for 600 mg/L Pb²⁺. During the intestinal stage, CP163 and CP51 still maintained adsorption efficiencies of 39.05% and 39.63% for 500 mg/L Pb²⁺. The study revealed that medium-molecular-weight pectins (CP163, CP51) demonstrated optimal adsorption performance in the gastrointestinal phases due to moderate degradation, which released active functional groups while maintaining structural stability. This research provides essential insights into the behavior of pectin in the human digestive system and offers a theoretical foundation for the development of oral heavy metal adsorbents.