The increasing prevalence of obesity and related diseases has made it imperative to address obesity as a pressing public health concern. Urgent attention is needed to develop innovative treatment options and strategies for obesity-related diseases. Fatty acid synthase (FAS) is a complex multiple enzyme that plays a critical role in the biosynthesis of long-chain fatty acids. Its dysregulation has been implicated in various human diseases, including obesity, type 2 diabetes, cancer, inflammation, and cardiovascular disease. Consequently, research on FAS inhibitors has received increasing attention over the past 30 years. In China, traditional Chinese medicines (TCMs) and functional foods are being recognized for their potential to alleviate disease status, particularly chronic diseases like obesity. Several TCMs have been found to have a strong inhibitory effect on FAS. This review aims to summarize the literature on the role of FAS as a biomarker and therapeutic target in obesity and related diseases while providing evidence to support the anti-obesity potential of TCMs and functional foods with FAS inhibitory activities.