There is strong correlation between antioxidant activity and hepatoprotector activities in vitro. Macaranga tanarius (MT) is abundant at East Kalimantan and the stems were proven to have antioxidant activity, but efficacy as hepatoprotector in vitro and active compounds is not known. The aim of this research is to examine the active fraction of M. tanarius as antioxidant and or hepatoprotector, also it’s active compounds. MT simplicia were macerated with methanol at room temperature for 3 days and repeated three times. The extracts were fractionated with increasing solvent polarity starting from n-hexane, dichloromethane, ethyl acetate (EtOAc), n-butanol and water. Crude extract and the five fractions were tested in vitro for antioxidant activity using radical scavenging activity assay using 2,2-diphenyl-1-picrylhidrazyl and hepatoprotector activity. Chromatogram profiles were done for the most active fraction using thin-layer chromatography silica gel 60 F254. Results showed the strongest antioxidant activity was EtOAc fraction with IC50 values (6.24 + 0.96) mg/mL and contained secondary metabolites polyphenols that proven having antioxidant activity. The strongest in vitro hepatoprotector activity was also EtOAc fraction with IC50 values (99 + 2) mg/mL. It can be concluded that EtOAc fraction of MT stems had antioxidant and hepatoprotector activity in vitro and contained secondary metabolites polyphenols with antioxidant activity.