| Summary: | In recent decades, a lot of attention has been paid to <i>Cannabis sativa</i> L. due to its useful applications, including in fibers, oil, food for humans and animals, and therapeutics. The present study aimed to determine antioxidant activity of cannabinoids in <i>Cannabis sativa</i> L. in vivo, evaluating the possible antioxidative effect of <i>Cannabis sativa</i> L. extract (CE) on malondialdehyde (MDA) and glutathione (GSH) concentrations as well as on catalase (CAT) activity in BALB/c mice. In total, 40 mice were divided into five equal groups: the aluminum group (7.5 mg AlCl<sub>3</sub>/kg/d (0.15 LD<sub>50</sub>), the saline group, the 10% ethanol group (an appropriate amount of the solution for mouse weight), the CE group (1.6 mg CE/g/day), and the aluminum-CE group (7.5 mg AlCl<sub>3</sub> plus 1.6 mg CE/g/day). The results of the study showed that CE significantly decreased (by 26.81%, <i>p</i> < 0.05) the concentration of GSH in blood of the mice and the concentration of MDA in the brain (by 82.12%) and liver (by 53.5%) of the mice compared to the respective concentrations in the AlCl<sub>3</sub> group. CE significantly (<i>p</i> < 0.05) increased CAT activity in the brain (by 64.79%) and liver (by 72.37%) of the mice after the AlCl<sub>3</sub>-induced prooxidant effect. The results showed the antioxidant activity of cannabidiolic acid (CBDA) in vitro. The findings in vivo indicate that <i>Cannabis sativa</i> L. is a good source of natural antioxidants and can be used in the management of oxidative stress.
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