Immunomodulators have the ability to either enhance or downregulate immune responses against pathogens, malignancies, and injury. In recent years, significant scientific interest has focused on natural and plant-based immunomodulators due to their long-standing use in traditional medicine systems and their comparatively fewer side effects. This comprehensive review examines the concept of immune modulation and critically evaluates key medicinal herbs known to influence immunity, including Withania somnifera, Tinospora cordifolia, Curcuma longa, and Ocimum sanctum. The roles of bioactive plant constituents such as alkaloids, flavonoids, terpenoids, and polysaccharides in modulating immune cells, cytokine production, and signaling pathways (e.g., NF-κB and MAPK) are discussed. Evidence from human studies, including Ayurvedic regimens for SARS-CoV-2 infection and Ashwagandha clinical trials, is reviewed along with safety, standardization challenges, and future research directions. Overall, plant-derived immunomodulators show promise, although robust clinical evidence and quality control are essential for their integration into modern healthcare.