Plant secondary metabolites or phytochemicals are essential to the effects of many contemporary medications and medicinal plants. Certain medicinal plants are well recognized as enchanted herbal treatments due to their ability to directly affect the pathogen and enhance the host's immunity. The chemical components derived from these botanicals, which are referred to as phytochemicals, were promising since they modulate lymphocytes, which lowers the risk of infection and strengthens the human immune system. For this reason, they are called immunomodulators. They have shown effective and significant therapeutic applications against diverse infections, diseases, disorders, etc. Along with these phytoimmunomodulators, miRNA from plants have also been studied for their involvement in various diseases. These small miRNAs have the ability to control target genes (mRNAs) by translational inhibition or cleavage. Researchers are having fascinating conversations as a result of the finding of plant-derived miRNAs that have the capacity to control mammalian gene expression across kingdom boundaries, which has been termed cross-kingdom gene regulation. Plant miRNAs can regulate endogenous mRNAs, thrive in the GI tract, and permeate the circulatory system after being ingested through food. In this review, we will focus on the role of phytoimmunomodulators and plant miRNAs in the physiological functions of the human body. We will also discuss the potential applications of plants in preclinical treatment.