Abstract: Background and Objective: Basil and ginger possess various beneficial effects such as antioxidant, anti-inflammatory and antimicrobial. However, studies on their bioefficacy do not consider changes to composition and chemical structure from processes such as digestion which may alter their bioactivity. The objective of this study was to evaluate the bioefficacy of bioaccessible fractions of basil and ginger in a HepG2 cell model before and after simulated in vitro digestion. Methodology: Digested and non-digested basil (BD and BND) and ginger (GD and GND) extracts were prepared and used for the determinations of Total Phenolic Content (TPC), Total Flavonoid Content (TFC), Ferric Reducing Antioxidant Power (FRAP), Oxygen Radical Absorbance Capacity (ORAC) Assay and Trolox Equivalent Antioxidant Capacity (TEAC). Lactate dehydrogenase (LDH) and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) were used as measures of efficacy. Glutathione (GSH) and Glutathione-S-Transferase (GST) were also determined. Results: Results showed that TFC was significantly (p≤0.05) increased after in vitro digestion while, a 3 fold decrease was noted in TPC. Antioxidant activities were also decreased after in vitro digestion. The BD extracts exerted significant (p≤0.05) cytotoxicity (LDH) and reduced (p≤0.05) cell viability (MTT) compared to cells treated with BND extracts. The reverse was however, observed in cells treated with GD and GND. LDH in cells treated with GND ranged from 5-53% and 6-67%, respectively for 12 and 24 h compared to cells treated with GD which ranged from 4-18% and 9-28%, respectively for 12 and 24 h. The GSH levels and GST activities were significantly (p≤0.05) higher in cells treated with BND extracts compared to cells treated with BD extracts. However, results varied with ginger extracts. Conclusion: Although, the results indicated that digested and non-digested extracts of basil and ginger induced cytotoxicity and reduced cell viability in HepG2 cells, the distinct differences in the level of efficacy may reflect alterations in the polyphenolic composition caused by the digestion process.