The marine bivalve Codakia orbicularis, harbors endosymbiotic bacteria located in its gill filaments. Bioassay-guided fractionation of an ethyl acetate extract of the gill tissues led to antibacterial fractions (against Gram positive and negative bacteria). The fraction eluted in AcOEt/ MeOH 90:10 displayed the greatest bioactivity. This fraction was analyzed using usual chromatographic and spectrometric methods and revealed three compounds. The first one (compound 1) was an acetamide isolated for the first time from the biosphere. The other two were mono-glycerolipids (compound 2) and (compound 3) with at the position sn-2 of their glycerol monounsaturated fatty acid chains (respectively C18:1Δ9 and C16:1Δ9). Compounds 2 and 3 showed bacteriostatic activity against two pathogenic Gram-negative bacteria using a disc diffusion assay method. These molecules have been isolated for the first time from a bivalve. Further investigations are currently in progress, so as to understand the role of these bioactive compounds into the regulation of C. orbicularis’ endosymbionts and/or to free-living pathogens.