Antioxidant-rich natural products can be included in the daily diet and represent a growing range of nutraceuticals. In search of effective nutraceutical agents, we studied the antioxidant potential of an herb, E. californicum, also known as yerba santa or “holy herb.” Ethanol extract of E. californicum leaves were screened for important classes of bioactive molecules. Total phenolic and flavonoid contents were quantified. Antioxidant capacity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and ferric reducing/antioxidant power (FRAP) assay. To explore the mechanism of action for antioxidant activity, the effect of the extract was studied on superoxide and hydroxyl radicals. Qualitative studies determined the presence of saponins, phlobatannins, phenols, tannins, terpenoids, cardiac glycosides, and steroids, and flavonoids in yerba santa. The leaves were found to be rich in phenol content (78.58 ± 0.016 μg GAE/mg) and flavonoid content (6.76 ± 0.003 μg QE/mg). At a concentration of 1.0 mg/mL, the extract showed 93.39% inhibition of DPPH radicals, 57.36% inhibition of superoxide radicals, and 80.89% inhibition of hydroxyl radicals. This study reveals that E. californicum leaves are a rich source of antioxidants and can be used as a nutraceutical.