Drepanoalpha® hard capsules, a dry ethanolic extract (drug-extract ratio, 100/11) of a mixture of Justicia secunda Vahl and Moringa oleifera Lam dried leaves (1: 1, w/w) are used for the management of sickle cell disease in the Democratic Republic of Congo. Aim of the study: This phytomedicine safety was investigated by acute and sub-acute administration in Guinea pigs. Materials and methods: Healthy, male and nulliparous and non-pregnant female Guinea pigs were obtained from Laboratory of Animal Experimentation and Toxicology of the Department of Biology, Faculty of Sciences, University of Kinshasa. The animals were randomly selected, marked and divided into 2 groups of 5 animals each (3 males and 2 females) and 4 groups of 3 animals each for acute and sub-acute toxicity studies, respectively. The contents of hard capsules were dissolved in normal saline solution (NaCl 0.9 %). Animals received by gavage a single dose of 5000 mg/ kg of body weight (B.W.) of Drepanoalpha® hard capsules (acute toxicity) and 125 mg/ kg, 250 mg/ kg and 500 mg/ kg of B.W. twice daily for 28 days (sub-acute toxicity). Normal saline solution was used as control. Hematological, biochemical and histopathological analyses were performed and the behavior of the animals was observed after treatment. Results: The median lethal dose (LD50) is higher than 5000 mg/ kg of B.W., and the relative weights of vital organs (kidneys, liver and heart) collected from Guinea pigs at the end of treatment on D14 (acute toxicity) and D28 (sub-acute toxicity) has not undergone significant changes (p > 0.05). The results of haematological (red and white blood cells counts, haemoglobin, haematocrit) and biochemical (ALT, AST, albumin, total protein) tests did not show significant differences between control and test groups (α=0.05 for acute toxicity), while the histopathological study revealed no damage to the various organs excised. Conclusion: The results indicate the safety of Drepanoalpha® hard capsules, confirming previous studies, in rats and Guinea pigs, based on aqueous decoction of its raw herbs mixtures and the corresponding lyophilizate. Keywords: Acute toxicity, Sub-acute toxicity, Drepanoalpha® hard capsules