We report the encapsulation of two grape pomace polyphenolic extracts into mesoporous MCM-41-type silica matrices (pristine and Zn or Mg heteroatom modified) to reduce the extract sensitivity and enhance its stability, while preserving the radical scavenger activity. Various grapes marc (Cabernet Saugvinon and Feteasca Neagra from the Black Sea region and commercially available grape skins powder) were used to prepare ethanolic extracts either through conventional extraction, or microwave-assisted procedure. The polyphenolic extracts composition was analysed by reversed phase-high pressure liquid chromatography and spectrometric determination of total polyphenols and ascorbic acid (using Folin Ciocalteu reagent), total flavonoids (by AlCl3 complexation), as well as total anthocyanin monomeric pigments content. The encapsulated extract into MCM-41 silica, as well as Zn-MCM-41 and Mg-MCM-41 matrices showed an enhanced radical scavenger activity assessed by DPPH procedure developed for solid samples. The cytocompatibility tests performed on HaCaT keratinocyte human cells demonstrated a good cytocompatibility for the Cabernet Saugvinon and grape skins extracts free and encapsulated into MCM-41-type matrices. Display omitted •Encapsulation for the first time of phenolic extract into MCM-41-type silica matrices.•Development of a procedure for radical scavenger activity for encapsulated extract.•Enhancement of radical scavenger properties of encapsulated phenolic extract versus the extract alone.•Assessment of cytocompatibility of free and encapsulated grape pomace extract.