The present work describes the protective effects of the crude Northeast Portuguese propolis enriched phenolic extract against staurosporine (STS) and hydrogen peroxide (H 2 O 2 )-induced neurotoxicity. These two stress inducers act through various pathways, including the production of reactive oxygen species (ROS) and the induction of apoptosis through caspases activation. STS (25 and 50nM) and H 2 O 2 (100μM) increased intracellular ROS and diminished cellular reducing ability in cultured cortical neurons, under conditions unrelated with massive loss of plasma membrane integrity, suggesting decreased neuronal function. Moreover, 25nM STS and 100μM H 2 O 2 increased caspase-3 activity by about 2.8- and 4.6-fold, respectively. Pre-treatment of cortical neurons with the ethanolic extract of propolis (EEP) in the range of 0.01–1μg/ml showed no protective effect on cell reducing capacity, but decreased H 2 O 2 -stimulated increment in ROS production by about 17%. In addition, the EEP attenuated STS- or H 2 O 2 -induced activation of caspase-3 by 23–39%. Overall, the results show moderate protective effects induced by Northeast Portuguese EEP in cortical neurons subjected to stress stimuli.