The genus Euphorbia is widespread and possesses medicinal uses. However, there isno available phytochemical information on Euphorbia serrata L. This study investigates thecomposition of the hydromethanolic extract of its aerial parts and proposes its utilization forcrop protection purposes, following integrated pest management guidelines. Gaschromatography-mass spectrometry results indicate that the primary phytocompounds include3-methylbutyl formate, quinic acid, N1-(4-hydroxybutyl)-N3-methylguanidine acetate, and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, which have antimicrobial activity. Suchactivity was tested against four diseases of borage (Borago officinalis L.), namely Pseudomonascichorii, Botrytis cinerea, Fusarium oxysporum, and Sclerotinia sclerotiorum. In vitro tests revealedminimum inhibitory concentrations (MICs) of 750 and 1000 μg·mL-1 against the bacterium andthe three fungal taxa, respectively. The antimicrobial activity was further enhanced bycombining the ex