In this study, silver nanoparticles (PE-AgNPs) were synthesized using Premna esculenta (PE) leaf extract, characterized by UV, TEM, TEM-EDX, XRD, DLS, and ICPOES studies. AgNPs were found to be stable at −35 mV with 26.157 ppm concentration. AgNPs were found triangular in shape with an average size of about 44 nm. Hepatoprotective activity was assessed in animal model using silymarin as standard drug. Biochemical parameters (serum AST, ALT, γGT, ACP, and ALP), inflammatory markers (IL 1β, IL 17, TNF α, and IL 10), and antioxidant markers (GSH, SOD, Catalase, and LPO) were assayed. Liver tissue was processed for histological analysis. Induction of hepatotoxicity increases AST, ALT, γGT, ACP, ALP, IL 10, LPO, and decreases IL 1β, IL 17, TNF α, GSH, SOD, and Catalase. PE-AgNPs treatment significantly decreases IL 10, LPO while IL 1β, IL 17, TNF α, GSH, and SOD were increased in animals. PE-AgNPs partially recovered CCl4-induced changes in liver histology.