Microbial infections and antibiotic resistance are two of the most serious threats to society's health today. Millions of people die each year as a result of microbial infections. In 2020, the COVID-19 pandemic caused by viral infections was responsible for the highest amount of all deaths that year. Existing antimicrobial drugs have become less effective, if not ineffective, as a result of the emergence of resistance. Several antibiotic resistance-fighting strategies have been proposed in recent years. One strategy proposed to achieve this objective has been to use combination therapy which appears to restore the desired antimicrobial activity. Several medicinal plants have demonstrated therapeutic effects against pathogens that cause human infections due to their phytochemicals constituents which have been elucidated to act as antimicrobial agents. This chapter focuses on phytochemicals as antimicrobial agents, giving information about infectious diseases and the pathobiology of these diseases. Also, the mechanisms of antimicrobial activity of phytochemical were discussed.