Flavonoids are a large class of small molecular secondary metabolic produced in different parts of plants. They perform a variety of physiological functions in various organs of plants and display a wide range of pharmacological or beneficial health effects for humans, which include antioxidative activity, free radical scavenging capacity, coronary heart disease prevention and antiatherosclerotic, hepatoprotective, anti-inflammatory and anticancer activities. Hence, flavonoids are gaining high attention from the pharmaceutical and healthcare industries. Notably, these compounds have been found to be a potent antimicrobial agent by destroying bacterial cell membrane, inhibiting synthesis of bacterial fatty acid, mucopeptide layer, nucleic acid, electron transport chain and ATP, as well as inhibiting the activity of bacterial metal enzyme. At the cellular level, they can also prevent bacteria from attaching to host receptors, and inhibit bacterial biofilm formation. They can not only selectively target bacterial cells but also inhibit virulence factors and other forms of microbial threats. Moreover, some plant flavonoids manifest the ability to reverse the antibiotic resistance and enhance action of the current antibiotic drugs.The development and application of flavonoid-based drugs could be a promising approach for antibiotic-resistant infections.