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Over the last few decades, Rumex species have been recognized as a promising source of new compounds with numerous pharmacological activities. Therefore, the antioxidant activity of Rumex tingitanus (R. tingitanus) leaves extracts was evaluated in vitro and then confirmed in vivo as well as the antidepressant-like and toxicological effects of the extracts. The ethyl acetate fraction (Rt EtOAcF) followed by hydroalcoholic extract (Rt EtOH-H2O) showed a remarkable in vitro antioxidant activity. The hydroalcoholic extract (Rt EtOH-H2O) showed significant hepatoprotective activity against carbon tetrachloride- (CCl4-) induced liver toxicity which is seen from inhibition of the malondialdehyde (MDA) accumulation and enhancement of the liver antioxidant enzymes activities. The Rt EtOH-H2O and Rt EtOAcF extracts were able to reduce the immobility time in mice and then elicited a significant antidepressant-like effect. The ethyl acetate fraction (Rt EtOAcF) was purified and resulted in the identification of a new antioxidant component called 4′-p-acetylcoumaroyl luteolin. The Rt EtOAcF and the 4′-p-acetylcoumaroyl luteolin revealed a strong antioxidant activity using DPPH test with IC50 of 11.7 ± 0.2 and 20.74 ± 0.6 μg/ml, respectively, and AAI of 3.39 and 1.92 better than that of BHT, used as control.