Glycation of proteins by reducing sugars produces toxic and immunogenic compounds called advanced glycation end products (AGEs). AGEs plays important role in the progression of typical diabetes complications. Silybum marianum L. contains powerful antioxidants that quench free radicals, which are unstable and reactive compounds that damage DNA and cellular structures. This study aimed to evaluate the antioxidant activities and the inhibitory effects of ethanol:water (1:1) extract of the Silybum marianum seed (Sly E) and silymarin (Sly) on fructose mediated protein glycation and AGE formation. The total amount of silymarin in Sly E was found to be 2.59 mg/gDW by HPLC. The composition of phenolic in the extract was found to be 262.70 µg gallic acid (GAE)/mg extract. The composition of flavonoids in the extract was found to be 10.50 µg quercetin (QUE)/mg extract. The seed exhibited ABTS radical cation decolourization inhibition with 70.4% at 300 mg concentration. Ferric reducing power of the extract was also evaluated. The SlyE and Sly also demonstrated strong inhibitory effects on the production AGEs in bovine serum albumin (BSA)/fructose model. Sly E and Sly has a significant effect in preventing oxidative protein damage, including the effect on the formation of fructosamines, α-dicarbonyls and protein carbonyl content (PCC). Sly E and Sly were able to prevent the glycoxidative damage of BSA. It can be concluded that the Sly E has antiglycating potential as well as antioxidant properties. [Display omitted] • Advanced glycation end products (AGEs) plays a role in diabetes-related complications. • The seed of extract of Silybum marianum L. contains many flavonoids and flavonolignans. (eg. silybin, isosilybin, silychristin, silydianin and taxifoline). • Silybum marianum L. extractwas found to have role in the prevention of early as well as advanced glycation end products. • Flavonoids present in milk thistle extract inhibited reactive oxygen species induced by AGEs. • Silybum marianum L. seed extract was able to prevent the glycoxidative damage of proteins. [ABSTRACT FROM AUTHOR]