Acid resistance (AR) is an indispensable mechanism for the survival of neutralophilic bacteria, such as Escherichia coli (E. coli) strains that survive in the gastrointestinal tract. E. coli acid tolerance has been extensively studied during past decades, with most studies focused on gene regulation and mechanisms. However, the role of cell membrane structure in the context of acid stress resistance has not been discussed in depth. Here, we provide a comprehensive review of the roles and mechanisms of the E. coli cell envelope from different membrane components, such as membrane proteins, fatty acids, chaperones, and proton-consuming systems, and particularly focus on the innovative effects revealed by recent studies. We hope that the information guides us to understand the bacterial survival strategies under acid stress and to further explore the AR regulatory mechanisms to prevent or treat E. coli and other related Gram-negative bacteria infection, or to enhance the AR of engineering E. coli.