Streptomycetes are mycelium-forming bacteria that produce two thirds of the clinically relevant secondary metabolites. Despite the fact that secondary metabolite production is activated at specific developmental stages of the Streptomyces spp. life cycle, different streptomycetes show different behaviors, and fermentation conditions need to be optimized for each specific strain and secondary metabolite. Cell-encapsulation constitutes an interesting alternative to classical fermentations, which was demonstrated to be useful in Streptomyces, but development under these conditions remained unexplored. In this work, the influence of cell-encapsulation in hyphae differentiation and actinorhodin production was explored in the model Streptomyces coelicolor strain. Encapsulation led to a delay in growth and to a reduction of mycelium density and cell death. The high proportion of viable hyphae duplicated extracellular actinorhodin production in the encapsulated cultures with respect to the non-encapsulated ones.