Abstract Sepsis is a severe reaction of the body to an infection, presenting a critical medical crisis. It represents an imbalance between the body’s anti- and pro-inflammatory reactions. The occurrence of sepsis, which leads to multiple-organ failure and increased mortality, is marked by dysfunction in the lungs, heart, kidneys, and liver. The involvement of reactive oxygen species is believed to contribute to the progression of sepsis. Data suggest potential advantages of phenolic compounds derived from plants in combating sepsis. Plant polyphenols can be antioxidants by scavenging free radicals, chelating metals, and binding to proteins. In this research, silver nanoparticles (AgNPs) were produced by the aqueous extract of Cichorium intybus leaf for the purpose of treating sepsis-induced DNA harm. The recent study focused on the biological aspect including the cytotoxicity properties on normal (HUVEC) cell line. The AgNPs were analyzed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), fourier-transform infrared spectroscopy, X-ray powder diffraction, and UV-Vis. The TEM and SEM images of AgNPs exhibited the average size of 35.29 nm with spherical morphology. In the in vivo study, the animals were categorized into four groups: sepsis-induced, sham, AgNPs-20, and AgNPs-100. AgNPs treatment resulted in a significant decrease in tissues damage (p < 0.01). The sepsis-induced group showed a significantly elevated malondialdehyde (MDA) level in comparison to the sham group (p < 0.01). Nevertheless, the groups that received AgNPs experienced a decrease in MDA levels and an increase in glutathione and superoxide dismutases levels (p < 0.01). Additionally, the rats treated with AgNPs exhibited a reduction in the IL-1β mRNA expression levels (p < 0.01).