A by-product is a secondary substance unintentionally produced during manufacturing and can be repurposed through recycling. In particular, by-products generated from the processing of natural materials are valuable because of their bioactive compound content, such as polyphenols and anthocyanins. Obesity is a global health issue, and medicines for obesity have side effects, such as insomnia and headaches. The demand for safe anti-obesity treatments based on natural products has increased. In this study, the anti-obesity efficacy of chestnut inner skin powder (CIS), a by-product, was investigated in a high-fat diet (HFD)-induced obesity model. CIS (100, 500, and 1000 mg/kg) was administered orally for 7 weeks, and 200 mg/kg garcinia was used as the positive control. Body weight (BW) and food intake were monitored weekly. Our results showed that CIS intake reduced BW, liver weight, white adipose tissue (WAT) weight (epididymal, retroperitoneal, and perirenal tissues), leptin levels, LDL-c levels, and expression of adipogenesis- and lipogenesis-related genes, similar to the positive control group. Additionally, CIS activated the AMPK/ACC signaling pathway in the liver and reduced adipocyte size in the WAT H&E stain. In conclusion, these findings suggest that CIS may prevent and treat obesity by regulating adipogenesis, lipogenesis, and lipid metabolism.