Background. Nowadays, the immunomodulatory properties of plants have been studied extensively with greater interest due to increasing awareness and combating the severity of immunomodulatory diseases.Scope and Approach. This paper highlights the efficacy of the available literature evidence on natural immunomodulators of plant origin and synthetic ones. In addition, several aspects of plants and their phytoconstituents responsible for immunomodulation have been discussed. Moreover, this review also discusses the mechanism involved in immunomodulation.Key Findings. One hundred fifty medicinal immunomodulatory plants are currently identified to find novel immunomodulatory drugs. Of these plants, the plant familyAsteraceaealso takes the first rank by offering 18 plant species (12%). Similarly of the plants studied so far, 40% belong to theAsteraceaefamily.Echinacea purpureaof this family is most known for its immunostimulating activity. The most prominent immune-active bioactive molecules are polyphenols, terpenoids, and alkaloids. Also, eight plant bioactive immunomodulators were checked for clinical trials and found in the market. These are six immunosuppressants, resveratrol, epigallocatechin-3-gallate, quercetin, colchicine, capsaicin, and andrographolide, and two immunostimulants, curcumin and genistein. Nowadays, there are a lot of polyherbal traditional medicinal products sold in the market and claimed to their immunomodulators. However, much work is still needed to find more active immunomodulatory agents. The mechanism by which immunomodulatory medicinal plant exert their effect is through the induction of cytokines and phagocyte cells and the inhibition of iNOS, PGE, and COX-2 synthesis.