Introduction: Plants containing β-sitosterol and oleamide are important for various diseases. So, Dillenia indica, D. obovata, and D. pentagyna were investigated for phytochemicals, cytotoxicity, and genotoxicity levels on peripheral blood mononuclear cells (PBMCs) and Hela cells. The protective effect of D. pentagyna extract on a HepG2 cell line was also investigated. Methods: Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) were used for phytochemical analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) and comet assays were performed for toxicity testing and protective effects against DNA oxidative damage. Results: The major components were oleamide and β-sitosterol at 38.464-58.247% and 5.585-6.887% with concentration and quantity of β-sitosterol at 0.2-0.37 mg/mL and 0.42-0.964 mg/g leaf. The D. indica, D. obovata, and D. pentagyna toxicities on PBMCs showed IC50 values at >430, >430, and 350 μg/mL respectively, with no significant DNA damage (P > 0.05) compared to the negative control group. All plant extracts showed toxic activity on Hela cell with IC50 values at <0.43 μg/mL and induced significant DNA damage (P < 0.05) compared to the negative control group. Conversely, the activity of the D. pentagyna extract indicated low cytotoxic activity against HepG2 (IC50>430 μg/mL), no significant (P > 0.05) DNA damage induction, significantly (P < 0.05) decreased DNA damage level, and tremendous antioxidant effect. Additionally, a combined mixture of all plants in an equal proportion revealed no IC50 value and insignificant DNA damage. Conclusion: All the studied species contained oleamide and β-sitosterol, with toxicity on Hela cells without toxicity on PBMC. The D. pentagyna species showed high antioxidant effects and no toxicity on HepG2.