Worldwide, infectious diseases consistently remained as one of the prime causes of mortality, endangering both economic stability and public health. An increased quest for alternative treatment agents has been motivated by the emergence of multidrug-resistant (MDR) bacteria and the sluggish pace of new antibiotic discoveries. Because of their antibacterial, antiviral, antifungal, and antiparasitic qualities, phytochemicals—a broad class of bioactive substances made by plants—have become attractive options for treating a variety of illnesses. This chapter provides a thorough overview of phytochemicals that may be used to treat infectious diseases. It examines their classifications, mechanisms of action, therapeutic options, biotechnology advancements, and challenges in clinical translation. Phenolics, flavonoids, terpenoids, alkaloids, and essential oils are given particular attention, along with how nanotechnology can enhance their pharmacokinetics and bioavailability.