Bisphenol A (BPA), which is used in a variety of consumer-related plastic products, was reported to cause metabolic disruption. Substitute compounds are increasingly emerging, but are not sufficiently investigated. In this study, we aimed to investigate the mode of action of BPA and four of its substitutes during the differentiation of human preadipocytes. Human preadipocytes were exposed to BPA, BPS, BPB, BPF, and BPAF, as well as the PPARγ-antagonist GW9662. After 12 days of differentiation, global protein profiles were assessed using LC-MS/MS-based proteomics.