Oomycetes such as Saprolegnia sp. are responsible for serious economic losses in aquaculture, the strategies for their control lead to concerns about their efficacy and environmental repercussions, so alternatives for their regulation are being sought. The aim of this study was to evaluate the in vitro susceptibility of 2 representative strains of Saprolegnia sp. toward 2,4‐dihydroxy‐5′‐prenyl‐dihydrochalcone (A); dihydrochalcone isolated from the Chilean shrub Adesmia balsamica; and their derivatives oxyprenylated (B‐‐G) with the purpose to develop naturally occurring products in order to cope with emerging resistance phenomena. The minimum inhibitory concentration (MIC) and minimum oomycetocidal concentration (MOC) values were then determined for the series of compounds tested, in comparison with the conventional fungicides bronopol® and fluconazole plus the natural compound safrole, by quantifying fungal growth. Significant growth inhibition was observed for prenylated derivatives B–G, evidencing dihydrochalcone E as the most active. This compound presented MIC and MOC values (0.24–0.26 μM and 0.30–0.33 μM, respectively) superior to those determined for commercial antifungal in both of the tested pathogenic strains.