Chronic hepatitis B (HBV) and C (HCV) remain major global health burdens due to high morbidity, treatment costs, and the emergence of antiviral resistance. Plant-derived compounds offer a potential alternative or complementary therapeutic approach. This study evaluated the antiviral effects of Azadirachta indica (neem) and Moringa oleifera (drumstick tree) leaf extracts on peripheral blood mononuclear cells (PBMCs) obtained from HBV- and HCV-infected patients. To determine and compare the phytochemical profiles of A. indica and M. oleifera leaf extracts and assess their antiviral activity through induction of apoptosis and necrosis in virus-infected PBMCs. Leaf extracts were subjected to phytochemical screening. PBMCs isolated from HBV- and HCV-infected patients were treated with each extract and analyzed by flow cytometry to quantify live, apoptotic, and necrotic cell populations. Statistical analysis was performed using one-way ANOVA with significance set at P < 0.05. Phytochemical analysis revealed that A. indica contained flavonoids, alkaloids, tannins, saponins, glycosides, and steroids, whereas M. oleifera contained flavonoids, alkaloids, and tannins but lacked glycosides and saponins. In HBV-infected PBMCs, A. indica significantly reduced live cell percentages from 24.3% to 11.35% and increased necrotic cells from 18.98% to 55.43%. In HCV samples, live cells decreased from 40.27% to 37.78%, while necrosis increased from 21.35% to 30.1%. M. oleifera demonstrated comparatively moderate effects consistent with its simpler phytochemical profile. A. indica exhibited strong antiviral potential, markedly enhancing necrotic responses in HBV- and HCV-infected PBMCs, while M. oleifera showed moderate activity. These results highlight the therapeutic promise of phytochemical-rich extracts, particularly A. indica. Further investigations-including in-vivo validation, dosage formulation, cost-effectiveness assessments, and evaluation of synergistic effects with existing antiviral therapies-are warranted to advance their development as complementary treatments for chronic viral hepatitis.