Actinomycetes are well known for their capacity to produce a wide array of specialized metabolites with diverse biological activities, making them a valuable resource for the discovery of novel biocontrol agents. In previous work, we screened a collection of 175 actinomycete strains isolated from diverse Sudanese soils for inhibitory activity against Phytophthora infestans, the causal agent of late blight disease in potato and tomato. Using a comparative metabolomics and genomics approach, we identified approximately 75 potentially active metabolites and prioritized 15 candidate compounds for further investigation. Commercially available or synthesized standards of these compounds were subsequently evaluated against different developmental stages of P. infestans, including mycelial growth and spore germination, resulting in six active compounds, namely actinomycin D, antimycin A, borrelidin, ikarugamycin, macbecin I, and myriocin. In addition, their antimicrobial spectrum was assessed against a panel of plant pathogenic oomycetes and fungi to determine whether their activity is broad-spectrum or target-specific. Antimycin A and macbecin I exhibited strong antifungal activity against Alternaria solani, whereas actinomycin D and myriocin showed moderate inhibitory effects. In contrast, borrelidin displayed pronounced anti-oomycete activity against Pythium ultimum, while ikarugamycin specifically inhibited the zoospore germination of P. infestans. Notably, none of the tested compounds showed activity against Rhizoctonia solani. To facilitate translation toward practical application of promising biocontrol strains in Switzerland, a Swiss collection of actinomycetes (n = 238) was evaluated both in vitro and in planta against P. infestans and additional phytopathogens. Future analyses will determine whether active strains from both (Sudanese and Swiss) collections share biosynthetic gene clusters and metabolites responsible for their antagonistic effect against P. infestans or whether they act through different mechanisms. Overall, this project aims to exploit the metabolic diversity of actinomycetes to develop effective and sustainable biocontrol solutions against late blight disease, contributing to environmentally friendly plant protection strategies.