The crude ethanolic extract from aerial parts ofPothomorphe umbellataL. (Piperaceae) and fractions obtained by partitions sequentially among water-methanol, methylene chloride, and ethyl acetate, as well as the major constituent, 4-nerolidylcatechol, were, respectively, evaluated and evidenced for antioxidant and cytotoxic effects through fluorometric microplate and microculture tetrazolium assays in HL-60 cells. The crude ethanolic extract demonstrated the preeminent antioxidant activity (IC50=1.2 μg/mL) against exogenous cytoplasmic reactive oxygen species, followed by the water-methanolic (IC50=4.5 μg/mL), methylene chloride (IC50=5.9 μg/mL), ethyl acetate (IC50=8.0 μg/mL), 4-nerolidylcatechol (IC50=8.6 μg/mL), and the sterol fractions (IC50>12.5 μg/mL). Vitamin C, the positive control used in this assay, presented IC50value equivalent to 1.7 μg/mL. 4-Nerolidylcatechol (IC50=0.4 μg/mL) and methylene chloride fraction (IC50=2.3 μg/mL) presented considerable cytotoxicity probably because of the presence of ano-quinone, an auto-oxidation by product of the catechol. Polar compounds, present in the ethanol extract, appear to increase the solubility and stability of the major active constituent, acting synergistically with 4-nerolidylcatechol, improving its pharmacokinetic parameters and increasing significantly its antioxidant activity which, in turn, suggests that the aqueous-ethanolic extract, used in folklore medicine, is safe and effective.