Introduced from South America in the 19th century as an ornamental aquatic plant, Ludwigia has since invaded almost every continent. L. grandiflora is widespread and invasive in France, forming dense aquatic stands, which cause major ecological and economic problems and reduce local biodiversity. The eradication of L. grandiflora is either very difficult or even impossible. The purpose of this study was the valorization of potential antibacterial and antioxidant compounds in the leaf extract of L. grandiflora using a bioassay-guided fractionation approach. Antibacterial activity was assessed using the disc diffusion and microdilution methods against 14 strains of Gram-positive and Gram-negative bacteria. Crude methanolic leaf extract showed strong activity against most of the tested strains, sometimes being more active than common antibiotics. Maximum antibacterial activity was measured against two pathogenic bacteria, Staphylococcus aureus and Salmonella enterica. The bioassay guided fractionation led to the isolation of several fractions more active than the crude extract; antibacterial activity of fraction (A) was 52% higher than that of the crude extract against S. aureus. The antioxidant activity was evaluated by the scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) and was expressed as EC50 (µg/mL), the extract dose required to cause a 50% inhibition. The fraction (A) exhibited a higher antioxidant activity (EC50= 6 µg/mL), as compared to the crude extract (EC50= 26.3 µg/mL) and the Trolox (EC50= 15.9 µg/mL), which was used as reference standard. RP-HPLC analysis showed that myricetin was the major phenolic compound. However, there was insufficient time to determine the active molecules. This innovative study, which allowed the submission of a patent, suggests that Ludwigia may be considered as an interesting source of antibacterial and antioxidant compounds for therapeutic uses and for the cosmetic and nutraceutical industries.