Background Combretum glutinosum is a plant whose leaves are consumed as a vegetable and used in traditional medicine for the treatment of microbial infections. Objective The present study was designed to identify the compounds in C. glutinosum leaves extracts, and evaluate its antimicrobial activity, antioxidant ability and its toxicity in Artemia salina larvae in vitro. Methods The aqueous and ethanol extracts obtained from the leaves of the plant as well as known compounds previously isolated and characterized from the leaves of C. glutinosum were tested on eleven different microbial strains. The antioxidant activity of the extracts was evaluated by the Ferric Reducing Antioxidant Power method and the larval toxicity on Artemia salina larvae was also detected. Phytochemical screening and HPLC-DAD-HRESI-MS analysis were performed on the extracts to characterize its chemical composition. Results When tested at a concentration of 20 mg?mL?1, the extracts of C. glutinosum leaves strongly inhibited the growth of the bacterial strains with an inhibition diameter ranging from 7.25 mm to 44 mm, superior to those of the positive controls (tetracycline at 30 μg?mL?1 and amikacin at 30 μg?mL?1), inhibition diameters from 15 mm to 33 mm. The evaluated larval toxicity demonstrated that it had no harmful effects on Artemia salina larvae. The extracts present a good antioxidant activity at a concentration of 0.17 and 1.33 mmol ascorbic acid (per gram of extract) for the aqueous and ethanol extracts, respectively. However, none of the compounds tested at 500 μg?mL?1 were able to show good activity on the 11 reference strains. Phytochemical analysis revealed the presence of alkaloids, polyphenols, steroids, triterpenoids, reducing compounds, etc. in both extracts. The HPLC-DAD-HRESI-MS analyses revealed 18 compounds in the ethanol extract, from which 3 were identified, 15 compounds in the aqueous extract from which 5 could be identified. Conclusion The present work has shown that C. glutinosum extracts can be a good source of antimicrobial agents. They also possess the antioxidant property with absence of toxicity on A. salina larvae. A further bio-guided study could allow the identification and isolation of the active ingredients.