Five glycosides (1-5) containing one novel aliphatic glycoside Luohanguonoside G (1), one new lignan glycoside Luohanguonoside H (2) and three known ones (3-5) were isolated from the fresh fruit extract of Siraitia grosvenorii (S. grosvenorii). Structurally, according to various spectroscopic techniques analysis, the new compounds 1 and 2 were elucidated as a rare seven-carbon heptane glucose glycoside and a lignan glycoside, respectively. Among 1-5, the lignan glycosides 3 and 4 have been reported in other plants but separated from S. grosvenorii for the first time. Additionally, a cytotoxicity and a hepatoprotective activity experiment were performed on compounds 1-5 to evaluate their preventing ability for liver disease. The results indicate that compound 5 exhibited significant hepatoprotective activities in comparison with bicyclol and compound 1-4 exhibited moderate activity for liver protection compared to model control group. This research firstly assessed the hepatic protection competence of the isolates from S. grosvenorii in vitro, providing evidence for the further investigation on the preventing potential of liver diseases of this plant.