Obesity is characterized as abnormal or excessive fat accumulation harmful to one’s health, linked to hormonal imbalances, cardiovascular illness, and coronary artery disease. Since the disease stems mainly from overconsumption, studies have aimed to control intestinal absorption as a route for treatment. In this study, chitosan-thioglycolic acid (CT) was developed as a physical barrier in the gastrointestinal tracts to inhibit nutrient uptake. CT exhibits a superior mucoadhesive property compared to chitosan both in vitro and in vivo for the ability to form disulfide bonds with the intestinal mucosa. For CT as a potential drug delivery platform, hesperidin, a herb for bodyweight control in traditional Chinese medication, is encapsulated in CT and can be released consistently from this absorption barrier. In animal studies, CT encapsulated with hesperidin (CTH) not only results in a weight-controlling effect but limits adipose accumulation by hindering absorption, suggesting a potential role in obesity treatment. Neither CT nor CTH exhibit cytotoxicity or produce adverse immunological reactions in vivo.