Background. Encelia canescens Lam is a plant traditionally used in Peru for medicinal purposes, and is attributed antioxidant properties, indicating that it could be used in the prevention of non-communicable diseases. Objective: This study aims to evaluate the protection of erythrocytes from lipoperoxidation and the anti-inflammatory effect of ethanolic extract of E. canescens leaves in mice. Materials and methods: Protection from lipoperoxidation was evaluated by inhibition of hemolysis and quantifying malondialdehyde (MDA) concentration against oxidative stress induced with hydrogen peroxide (H2O2) at 200, 150, 100, 50 and 25 μg/mL E. canescens concentrations. The 1% carrageenan-induced air pouch model was used for evaluated inflammation, where albumin, total proteins, MDA, number and leukocyte differentiation were determined in the exudate, and a histopathological evaluation was performed. The concentrations evaluated were 100, 250 and 500 mg/kg of E. canescens Results: All the concentrations evaluated protected protected erythrocytes from lipoperoxidation (p<0.05), being E.D. value 200 μg/mL. Regarding anti-inflammatory effect, the albumin, total proteins and MDA values of the treatment groups were lower than carrageenan 1% group (p<0.05), but, due to less leukocyte migration and presence of macrophages and the histopathological evaluation, the E.D value was 500 mg/kg. Conclusion: Ethanolic extracts of E. canescens leaves protect erythrocytes from lipoperoxidation and have dose-dependent anti-inflammatory effects maybe for presence of p-hydroxyacetophenone-derived, and these could be new safer anti-inflammatories.