Silkworm rearing activities ceased in the 1970′s in several European countries. Attempts on the re-establishment of ecological and sustainable sericulture in Slovenia and Hungary are ongoing. The aim of the study was to assess the usability of locally adapted mulberry genotypes for sericulture and to estimate connections between leaf compound and silkworm performance parameters. A controlled feeding experiment of silkworms was performed to test the influence of leaves from selected trees on the growth of larvae, the health and microbiological status of larvae (e.g., gut bacterial microbiome, Bombyx mori nucleopolyhedrovirus infection), weight of cocoons and raw silk parameters. The Slovenian and Hungarian mulberry genotypes had significantly higher total protein contents, and lower total phenolic contents and differed significantly in some individual phenolics compared to the reference sericultural and fruit varieties. Significant differences were found in the contents of the macro- and microelements, namely S, Mn, Fe, and Sr. Based on correlative statistics and multivariate analysis, a combined positive influence of proteins, specific phenolics, and microelements on larval growth and silk thread parameters was predicted. The results of the study indicate that selected local Slovenian and Hungarian mulberry varieties are suitable for high-quality silk cocoon and raw silk production.