A systematic literature review on immunomodulatory herbs of Ayurveda was conducted to explore their clinical potential. A variety of plant-based principles with potential immunomodulatory action have been identified, which may explain and justify their usage in traditional medicine in the past and can also serve as a foundation for future studies. This review aims to highlight the findings of research on plant-derived immunomodulators. Focusing the ethnopharmacological usage, the most relevant articles were chosen from the authentic databases of biomedical sciences. Different scientific online databases including Academic Search Premier, Embase, PubMed, Biological Abstracts, PLOS, Natural Standard, and Web of Science were used to conduct the present systematic literature search. Many plants, as well as certain phytoconstituents, have been implicated in the present study. The study also focuses on the mechanism of action of different plant medicines. The present review would be helpful in designing new research studies on medicinal plants with immunomodulatory properties.