Sepsis is a metabolic and systemic inflammatory response to infection. Morbidity and mortality of septic patients has not been changed with conventional therapy. In addition, clinical trials in sepsis have failed. Natural medicine is an important source on developing of new anti-inflammatory agents for infectious diseases. We performed a search from 2005 to 2017 on Medline-PubMed database. We selected studies that evaluated the therapeutic potential of medicinal plants or herbal mix in polymicrobial sepsis by cecal ligation and puncture (CLP). We identified 19 medicinal plants and herbal mix used to treat animals in polymicrobial sepsis model. Medicinal plant administration promotes immunomodulatory actions through receptors, cytokines, biomarkers of injury tissue, leukocyte migration and apoptosis of lymphocytes. In addition, survival rate was improved after medicinal plants treatment. New approaches using medicinal plants in polymicrobial sepsis could improve healthcare conditions in many countries because natural products are promising candidate against infectious diseases.