Inflammation and redox imbalance are related to the pathogenesis of chronic age-related diseases. For this reason, understanding the role of specific food-derived molecules on the regulation of their specific pathways is a relevant issue. Firstly, we showed that K-8-K and S-10-S, milk and soy-derived bioactive peptides, respectively, exert antioxidant effects through activation of the Keap1/Nrf2 pathway. Then Nrf2/HO-1 axis was investigated in order to understand if these peptides, besides their antioxidant activity, could exert anti-inflammatory effects in human cells. An increase of HO-1 expression in Caco-2 cells treated with K-8-K and S-10-S was observed. Moreover, when cells are treated with the two peptides and stimulated by TNF-α, the levels of NF-κB in the nucleus decreased. In the same conditions, pro-inflammatory cytokines gene expression was downregulated (IL1B, IL6 and TNF), while IL1RN gene, an anti-inflammatory cytokine, was upregulated. Then, when the cells were pre-treated with the two peptides and stimulated with LPS, a lower secretion of TNF-α was estimated in the supernatant of cells. In conclusion, these observations confirmed that Nrf2-activating bioactive peptides, K-8-K and S-10-S, exerted anti-inflammatory effects by inhibiting the NF-κB pathway.