The antioxidant capacity of phenolic compounds in red wine is suggested to be responsible for their health-promoting effects. Compared to other wines, little information is available on phenolic compositions and antioxidant capacity of Australian wine. Information related to the fate of these phenolics in the body once consumed is also very limited. The overall aim of this research was to investigate the relevance of red wine consumption as a source of health-giving antioxidants in humans. The phenolic composition of wine was determined using the Folin-Ciocalteu (total phenolic), aluminium chloride (total flavonols), methyl cellulose precipitation (MCP) (total tannins), pH differential (total monomeric anthocyanins), bisulfite bleaching (total polymeric anthocyanin fractions), and liquid chromatographic (LC-MS) (individual phenolics) methods. Antioxidant activities were measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis-93-ethylbenzthiazoline-6-sulfonic acid (ABTS) and oxygen radical absorbance capacity (ORAC) assays. The phenolic and antioxidant data were then used to establish the relationship between these two parameters in wines from different varieties (Shiraz, Cabernet Sauvignon and Merlot) and winemaking stages (crushing, fermentations, oaking and bottling). By using an in vitro digestion model that mimics the upper gastrointestinal tract (GIT) digestion, the stability of the wine phenolics during digestion was examined. Finally, to gain a better understanding of the post-digestion absorption of wine phenolics, their permeability across Caco-2 cell monolayers was evaluated. A total of 8 monomeric anthocyanins and 17 other phenolic compounds were positively identified in the red wines using LC-MS analysis. Most of the phenolic categories showed some positive correlations with the antioxidant activities but none of the individual phenolic compounds showed a strong correlation with the total antioxidant activity of the wine, implying a combined contribution of many wine phenolics to antioxidant effects. The phenolic compositions and antioxidant activities of three of Australia’s most common red wines varieties - Shiraz, Cabernet Sauvignon and Merlot were not different from each other, possibly due to the variability within each grape cultivar. During the winemaking process, the total phenolic content and the associated antioxidant activity of the wine increased during the fermentation process, as more phenolics are being extracted from grape skin, seeds and stems into the wine. During oak and bottle ageing, the total phenolic contents were stabilised. Most of the wine phenolics were more stable under acidic conditions (pH 2 and 5.5) than neutral or alkaline conditions (pH 7.4 and 9). This may partly explain the stability of the wine phenolics subjected to the acidic (pH 2) gastric digestion and their loss following simulated pancreatic digestion (pH 7.4). In addition, sample pre-treatment procedures prior to LC-MS analysis may have removed some antioxidants in the form of degradation products and/or new polymeric compounds following the in vitro gastric and pancreatic digestion processes. The missing products appeared to be detected by both the Folin-Ciocalteu method and ORAC assay, which measured the phenolic compounds and their antioxidant activity, after the pancreatic digestion. This suggests that the instability of phenolic compounds at pH 7.4, results in the transformation of most of the oral phenolic antioxidants into more stable forms in the GIT, which in turn contribute positively to the overall antioxidant activities of the ingested wine. All of the original wine phenolics had very low permeabilities across Caco-2 cell monolayers, except for syringic acid, p-coumaric acid and an unknown phenolic acid. Limited surface area for absorption (0.33 cm2) and the limited peak detection sensitivity in the LC method may have contributed towards the difficulty in detecting and identifying compounds with low permeability. In addition, extensive metabolism of absorbed phenolics by the Caco-2 cells may occur based on the appearance of several new peaks. However, due to their low concentrations and lack of reference, the identities of the new products and metabolites remain unknown. The present in vitro study suggests that upon ingestion, most of the original phenolic compounds in red wine are lost either through degradation to new compounds and/or complexation with other compounds. However, these products seem to possess some antioxidant activity and may be the key compounds responsible for the health-promoting effects of red wine. The limitation of the present study in detecting and fully identifying these breakdown products and metabolites should be addressed in future studies.