Immunomodulatory and immunocorrective therapies are important approaches to foster immunity. Biologically active substances (BAS) of plants, exhibiting a wide spectrum of pharmacological activity, can act as agents mobilizing the immune system. Plants belonging to the Caryophyllaceae family, including Silene sendtneri and S. roemeri, are rich in ecdysteroids and flavonoids, the compounds characterized by a large variety of biological activities with potential impact on the human immune system. In this study, the effect of native and chlorophyll-free plant extracts of S. sendtneri and S. roemeri on human monocyte-derived macrophages was examined. The production of cytokines was assessed using ELISA. Gene expression microarrays and RT-qPCR analysis were used to determine differentially expressed genes under the influence of the extracts. The results of the experiments showed that the extracts increased production of an M2-associated chemokine CCL-18 in macrophages. In addition, they induced the production of proinflammatory cytokines (TNF-α, IL-1β, and IL-6). The identified activity was detected both in native and chlorophyll-free extracts. Furthermore, plant extracts of S. sendtneri and S. roemeri influenced the expression of the CCL2, MMP9, VEGFA, and S100A9 genes in human macrophages. Overall, extracts of the Silene genus plants showed immunomodulatory effects by influencing macrophage activation in vitro.