Obesity has become a significant global public health issue. Previous studies have found that the Chenpi has the anti-obesity activity. However, the anti-obesity phytochemicals and their mechanisms are still unclear. This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking. A total of 17 bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified. The KEGG pathway analysis showed that the PI3K/Akt signaling pathway, MAPK signaling pathway, AMPK signaling pathway, and nuclear factor kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi. According to molecular docking analysis, the phytochemicals of Chenpi can bind to central anti-obesity targets. Based on the ADMET analysis and network pharmacology results, tangeretin exhibited the lowest predicted toxicity and potential for anti-obesity effects. In the in vitro lipid accumulation model, tangeretin effectively suppressed the free fatty acid-induced lipid in HepG2 cells by upregulating the PI3K/Akt/GSK3β signaling pathway based on the result of q-PCR and Western blotting. The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi, also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.