Oxidative stress is a major contributor to the pathogenesis of neurodegenerative diseases, such as Alzheimer´s disease. Cannabis sativa L. has gained increasing attention for its diverse bioactive compounds, especially those with antioxidant potential that could prevent oxidative stress. This study aimed to evaluate the antioxidant and neuroprotective properties of four full-spectrum extracts obtained from the female inflorescences of C. sativa L. with different chemotypes. First, we determined the total polyphenol content and the antioxidant capacity of the resins using DPPH, reducing power, and hydroxyl radical scavenging assays. To evaluate their neuroprotective activity, we pre-treated the HT-22 neuronal cells with subtoxic concentrations of two selected resins before glutamate exposure to induce neurodegeneration. We demonstrated that pre-treatment with these resins improved cell viability and reduced glutamate-induced apoptosis. Moreover, we found that the full-spectrum resins restored the ∆ѱmit and ROS levels modified by glutamate in the cellular model. These findings suggest that full-spectrum resins of C. sativa L. exert antioxidant and neuroprotective properties in vitro, supporting their potential as promising sources of compounds with beneficial effects on human brain health.