The emergence of multidrug resistant bacterial pathogens and the increase of antimicrobial resistance constitutes a major health challenge, leading to intense research efforts being focused on the discovery of novel antimicrobial compounds. In this study, endophytes were isolated from different parts of Sandwithia guyanensis plant (leaves, wood and latex) belonging to the Euphorbiaceae family and known to produce antimicrobial compounds, and chemically characterised using Molecular Network in order to discover novel antimicrobial molecules. One fungal endophyte extract obtained from S. guyanensis latex showed significant antimicrobial activity with Minimal Inhibitory Concentration on methicillin-resistant Staphylococcus aureus at 16 µg/mL. The chemical investigation of this fungus (Lecanicillium genus) extract led to the isolation of 5 stephensiolides compounds, four of which demonstrated antibacterial activity. Stephensiolide I and G showed the highest antibacterial activity on MRSA with a MIC at 4 and 16 µg/mL respectively.