Toll-like receptors (TLRs), a major component of innate immune system, are expressed as membrane or cytosolic receptors on neutrophils, monocytes, macrophages, dendritic cells (DCs), B lymphocytes, Th1, Th2, and regulatory T lymphocytes. It recognizes pathogen-associated molecular patterns (PAMPs) and Toll-interleukin1 (IL-1) receptor (TIR) of various invading pathogens. Downstream signaling of TLRs activates NF-κB, which acts as a transcription factor of pro-inflammatory cytokines, chemokines, and costimulatory molecules. A balance between pro-and anti-inflammatory cytokine protects host body from infectious agents and also induces the healing process. Some of parasitic infections by protozoans and helminths such as Malaria, Leishmaniasis, Trypanosomiasis, Toxoplasmosis, Amoebiasis, Filariasis, Schistosomiasis, Ascariasis, Taeniasis, and Fasciolosis are the leading cause of death and economic loss in both developing and developed nations. Frequent exposure to parasites, immigration, refugee resettlement, increasing immunodeficiency, climate change, drug resistance, lack of vaccination, etc. are the major cause of emerging and re-emerging of the above-stated diseases. However, TLR activation by parasites could stimulate antigen presenting cells and ultimately clear the pathogens by phagocytosis. So, a better understanding of host-parasite interaction in relation to TLR signaling pathway will improve the controlling method of these pathogens in immunotherapy.