Compartmentalization is a crucial feature of a natural cell, manifested in cell membrane and inner lumen. Inspired by the cellular structure, multicompartment polymersomes (MCPs), including membrane-compartmentalized polymersomes and lumen-compartmentalized polymersomes (polymersomes-in-polymersomes), have aroused great expectations for biological applications such as biocatalysis and cell mimics in the past decades. Compared with traditional polymersomes, MCPs have advantages in encapsulating multiple enzymes separately for multistep enzymatic cascade reactions. In this review, first, the design principles and preparation methods of membrane-compartmentalized and lumen-compartmentalized polymersomes are summarized. Next, recent advances of MCPs as nanoreactors and cell mimics to mimic subcellular organelles or artificial cells are discussed. Finally, the future research directions of MCPs are prospected.