Epigallocatechin gallate (EGCG), the predominant catechin in green tea, displays strong antioxidant and cytoprotective properties; however, its poor stability and limited oral bioavailability significantly restrict its therapeutic potential, prompting the need for new therapeutic strategies. Here, we reported synthesis and physicochemical characterization of chitosan nanoparticles (Ch-NPs) encapsulating EGCG (Ch-EGCG-NPs) by the ionic gelation method. The Ch-EGCG-NPs displayed tunable particle size (184-236 nm), narrow polydispersity, and positive zeta potential, supporting colloidal stability and efficient EGCG loading. NPs uptake was followed by confocal microscopy and flow cytometry, using FITC-labeled Ch-NPs demonstrating efficient internalization in pancreatic and hepatic cancer cell models, i.e HepG2 and PANC-1 respectively. In vitro assays revealed that Ch-EGCG-NPs preserved cell viability under hydrogen peroxide-induced oxidative stress and significantly modulated intracellular ROS levels. The oxidative treatment induced a 1.89-fold increase in ROS production compared to the control (corresponding to an 89% up-regulation), representing the largest percentage change observed. Conversely, Ch-EGCG-NPs markedly reduced ROS accumulation compared to free EGCG, lowering ROS levels from 2.24 to 1.06 (≈52.7% reduction) and from 2.24 to 0.66 (≈70.5% reduction), with reductions ranging from 52% to 70.5% in PANC-1 cells and up to 60.3% in HepG2 cells.