Siraitia grosvenorii (Swingle) is one kind of medical and edible plants with various health-promoting properties. Recently, its hypoglycemic and antidiabetic activities have been reported, but the underlying mechanism remains to be explored. The current study was aimed to investigate the antioxidant and antiglycation activities of mogroside extract (MGE) from Siraitia grosvenorii (Swingle). The results showed that compared to glycated BSA, MGE at middle (125μg/mL) and high dose (500μg/mL) significantly inhibited BSA glycation evidenced by decreased fluorescent AGEs formation, protein carbonyls and Nε-(carboxymethyl) lysine (CML) level at 500μg/mL by 58.5, 26.7 and 71.2%, respectively. Additionally, the antiglycative activity of MGE (500μg/mL) was comparable to aminoguanidine (AG) at the equal concentration. However, the inhibitory effect of MGE on glycation-induced increase of fructosamine level and decrease of thiol level was not remarkable. MGE was a potent peroxide radicals scavenger (851.8μmol TE/g), moderate DPPH and ABTS radicals scavenger with IC50 1118.1 and 1473.2μg/mL, respectively, corresponding to positive controls ascorbic acid of IC50 9.6μg/mL, and trolox of IC50 47.9μg/mL, respectively, and mild reducing power. These findings suggest that MGE may serve as a new promising antiglycative agent against diabetic complications by inhibiting protein glycation and glycoxidation.