Objective: This work is the first to investigate the in vitro anti-acne and cytotoxic activities of the leaves of Ludwigia peploides. With its important seasonal biomass production, this plant has great potential in several therapeutic and cosmetic applications. Methods: The antibacterial activity of the extract was screened against a consortium of skin microorganisms that cause acne vulgaris disease, using disc diffusion and broth microdilution methods. The antioxidant activity of methanolic leaf extract of L. peploides was evaluated by DPPH and NBT assays to assess the free radical scavenging activity of L. peploides, which in turn has a great importance related to its role in minimizing the oxidative stress linked to the pathophysiology of diseases like acne vulgaris. Its putative cytotoxicity was examined against human macrophage-like monocytic leukemia (THP-1) and human keratinocytes (HaCaT) cell lines. In addition, antiproliferative activity was screened against B16 cancer cell lines. Results: The extract displayed antioxidant effect by DPPH (IC50= 58 ± 6.0 µg mL-1) and NBT (IC50= 30 ± 2.8 µg mL-1) assays, and it was not toxic on HaCaT cells (IC50 > 200 µg mL-1). A strong inhibitory activity against Propionibacterium acnes (MIC = 1.9 µg mL-1) was registered for the extract, which had a bactericidal effect against Staphylococcus aureus, Staphylococcus epidermidis, and Salmonella enterica. Finally, the extract was shown to have an antiproliferative activity (IC50=5.5 ± 2.3 µgmL-1). Conclusion: The extract displays antioxidant and anti-acne effects as well as inhibition potential of B16 melanoma cells proliferation.