The antibiotic resistance in pathogenic bacteria is a major concern and the emergence of novel multidrug-resistant (MDR) strains are a growing threat worldwide. Bacterial resistance to antibiotics has become a serious problem of public health that concerns almost all antibacterial agents and that manifests in all fields of their application. Therefore, novel antimicrobial compounds against new bacterial targets and drug resistance mechanisms are urgently needed. Plants are well-known sources of structurally diverse phytochemicals such as alkaloids, flavonoids, phenolics, and terpenes, which plays important roles in human health. Plant-derived antimicrobial agents are an attractive and ongoing source of new therapeutics. Natural compounds that prevent and treat infections through dual action mechanisms such as oxidative stress against pathogens and antioxidant action in the host cell hold promising potential for developing novel therapeutics. Identification of detailed mechanisms of action of such Phyto molecules with both antioxidant and antimicrobial activities may help to develop novel antimicrobial therapeutics and benefit overall human health. The purpose of this chapter is to summarize important antioxidant phytochemicals and focusing on their potential role in the management of drug-resistant bacterial infections.