The fungal endophyte was isolated from the medicinal plant E. hirta was identified as Chaetomium sp. and the gene sequence has been submitted in NCBI with an accession number MF192757. The butanolic extract, dichloromethane and the methanolic extract of Chaetomium sp. showed significant antioxidant activity using DPPH radical scavanging method, and potential hepatoprotective activity compared with the standard silymarin. Hepatoprotectivity of methanolic, dichloromethane and butanolic extracts of Chaetomium sp. was evaluated by MTT assay in HepG2 cells with CCl4 induced toxicity and subsequently evaluated for cell viability. Antioxidant activity was demonstrated by DPPH radical scavenging assay. Quantification of total phenolic content was assessed by spectroscopic methods. The hepatoprotective activity of the butanolic, dichloromethane and methanolic extract was 61.93±1.477%, 62.19±0.9333% and 70.49±1.661% of cell viability at a concentration of 150μg/mL whereas the standard silymarin showed 93.26 ± 0.784%. The antioxidant activity of butanolic, dichloromethane and methanolic extracts of Chaetomium sp. is ranging from 50.39±1.060 to 69.63±0.452 with 41.29±0.769 mgGAE/g total phenolics, 55.14±2.135 to 55.14±2.135 with the total phenolic content of 69.78±0.615 mgGAE/g and 62.95±0.756 to 83.65±1.972 with the total phenolic content of 98.31±0.905 mg GAE/g. Ascorbic acid, BHT (butylated hydroxyl toluene) Gallic acid and Pyrogallol were used as standards which showed 98.37±0.763; 97.08±0.636; 94.89±1.103 and 96.98±0.098 reducing potential respectively. © 2018 Research Journal of BioTechnology. All Rights Reserved.