The emergence of antimicrobial resistance (AMR) of bacteria leads to a decrease or even failure in the effectiveness of antimicrobial treatment, poses a huge challenge to clinical anti-infective treatment, and seriously threatens human life. Therefore, coping with AMR of bacteria has become a major challenge and research hot spot in the field of global public health. Due to the wide sources and diverse biological activities, natural compounds play an important role in the practice of "reduction of antimicrobial agents, replacement for antimicrobial agents, and free of antimicrobial agents" in the breeding industry. In recent years, studies have discovered that a variety of natural compounds can serve as enhancer for antimicrobial agents, and the combined use of natural compounds with antimicrobial agents can restore the antimicrobial sensitivity of antimicrobial-resistant bacteria and enhance antimicrobial effects. This indicates that natural compounds have the potential to serve as new strategies in coping with AMR of bacteria. This paper reviews the synergistic antibacterial mechanism of natural compounds combined with antimicrobial agents based on the main resistance mechanisms of bacteria, and looks forward to their application prospects and challenges, in the hope of providing new ideas and strategies for coping with the crisis of bacteria AMR.