Medicinal plants such as Senna italica are increasingly used for their purgative virtues to treat stomach aches, fever, and jaundice. This study aims to screen the phytochemical compounds and to assess the antioxidant activity in vitro and the acute oral toxicity in vivo of Senna italica leaves. The plant was harvested, dried, pulverized, and preserved. Phytochemical screening was performed using different laboratory protocols. Ethanolic and aqueous extracts were, respectively, obtained by maceration and decoction technics. The assay for free radical scavenging was used to examine the antioxidant activity using DPPH. Acute oral toxicity was performed with aqueous and ethanolic extracts at 5000 mg/kg of body weight on female albinos Wistar rats, weighing 152.44 ± 3.68 g. Subjects were checked for any signs of mortality and macroscopy toxicity during the 14 days of the study. Biochemical and hematological parameters were measured to assess liver and kidney functions, and histological analysis of these organs was conducted. Phytochemical analysis highlighted the presence of total phenols, flavones, tannins, alkaloids, and quinone derivatives. Semiethanolic (78 μg/mL), ethanolic (9.7 μg/mL), and aqueous extract (9.2 μg/mL) showed an interesting antioxidant activity. Biochemical and hematological parameters were normal and not significantly different ( p > 0.05 ). The plant extracts did not produce any toxic effect or mortality at the provided dose. Senna italica extracts induced an increase in the volume of liver and kidney tissues but no necrosis. Thus, lethal dose 50 of Senna italica leaf extract is probably higher than 5000 mg/kg.