© 2018 Pharmacognosy Research | Published by Wolters Kluwer - Medknow. Background: Cancer is considered a serious public health problem in the world; searching alternative treatments of medicinal plants constitute a promissory field to find new anticancer drugs. Objective: The aim of this study is to evaluate the phytochemical screening, total phenolic content (TPC), antioxidant, and cytotoxic activity of ethanol extracts of Waltheria ovata (WO), Piper aduncum (PA), Myrciaria dubia (MD), Physalis peruviana (PP), and Geranium dielsianum (GD) on human tumor cell lines. Materials and Methods: Phytochemical screening was assessed using chemical reactives. TPC was developed using Folin Ciocalteu reactive, and the antioxidant activity was determined against 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals by spectrophotometry. The cytotoxic activity was determined on human tumor cell lines followed as: MCF-7, H-460, HT-29, M-14, K-562, and DU-145. Results: Phytochemical study confirmed flavonoids and phenolic compounds in all extracts. TPC was found to be the highest in WO extract (1250 mg of gallic acid equivalent/g of dried extract) rather than other extracts. The highest antioxidant activity was stablished in WO extract for DPPH and ABTS radical scavenging tests (inhibitory concentration [IC50] = 0.89 ± 0.01 μg/mL, IC50 =4.20 ± 1.50 μg/mL). Ethanolic extracts (μg/mL) showed low cytotoxicity on human tumor cell lines (CI50>20 μg/mL) for PA, PP, GD, MD. Meanwhile, WO presented cytotoxicity on H460, MCF-7, and K562 tumor cell lines. Conclusion: In our findings, WO and MD extracts revealed a high antioxidant and TPC. WO exhibited better cytotoxic effect compared with 5-FU. Hence, these medicinal plants could be effective to prevent cancer disease and oxidative stress. Abbreviations Used: IC50: Half inhibitory concentration. TPC: Total phenolic content. DPPH: ,2-Diphenyl-1-picrylhydrazyl. ABTS: 2,2-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid). AA: Ascorbic acid.