Objective: To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia (P. daemia) against anti-tuberculosis drugs (ATDs) induced liver injury. Methods: Wistar albino rats were divided into seven groups of six animal in each. The ATDs and P. daemia extract (100, 200 and 400 mg/kg, p.o.) were conjointly administered for 8 weeks and various biochemical, histoarchitectural, ultrastructural studies were performed. Results: Administration of ATDs significantly increased aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, cholesterol, bilirubin and decreased glucose and albumin level. Increased lipid peroxidation and reduction in glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were found after ATDs exposure. Administration of P. daemia extract maintained serum biochemical indices as well as antioxidant status similar to control and diminished oxidative stress in dose dependent manner. Histological and ultra-structural observations substantiated biochemical findings. Conclusions: P. daemia has therapeutic potential against ATDs induced liver injury and may be of clinical significance after extensive studies.