Background: Dysregulation of inflammation underpins chronic cardiovascular, metabolic, neurodegenerative, and neoplastic conditions. Traditional medicine has long utilized medicinal plants to alleviate and treat systemic inflammation. Specifically, Rhodiola rosea L. and Rhodiola quadrifida (Pall.) Fisch. & C.A.Mey. possess anti-inflammatory, antitumor, antioxidant, and anti-angiogenic properties. Saposhnikovia divaricata (Turcz.) Schischk. has been shown to exert anti-inflammatory effects, support musculoskeletal function, and enhance tissue regeneration. Furthermore, Salsola laricifolia Litv. has been studied for its antioxidant, immunomodulatory, and anti-inflammatory activities. Although the individual anti-inflammatory, antioxidant, and antitumor activities of these plants are established, research evaluating the combined effect of their combined extract remains scarce, providing the rationale for this study. Aim: To evaluate the in vitro effects of a combined extract derived from these medicinal plants on the expression of selected pro-inflammatory cytokines. Materials and Methods: A dry combined extract consisting of Rhodiola rosea, Rhodiola quadrifida, Salsola laricifolia, and Saposhnikovia divaricata was prepared at the Chemistry and Technology Sector of the Institute of Pharmaceutical Research, Monos Group. An in vitro inflammation model was established using murine RAW264.7 macrophage-like cells stimulated with lipopolysaccharide (LPS, 100 ng/mL). Cell viability was assessed using the CCK-8 assay, while the output of pro-inflammatory cytokines TNF-α and IL-6 was measured via Enzyme-Linked Immunosorbent Assay (ELISA). Statistical analysis was performed using one-way ANOVA. Result: The combined plant extract demonstrated no cytotoxic effects on RAW264.7 cells across the tested concentration range. In LPS-stimulated RAW264.7 macrophages, the composite extract dose-dependently and significantly suppressed the production of the pro-inflammatory cytokines TNF-α (p<0.001) and IL-6 (p<0.0001). Conclusion 1. The combined extract of Saposhnikovia divaricata, Rhodiola rosea, Rhodiola quadrifida, and Salsola laricifolia exhibited no cytotoxicity in vitro within the range of 50–400 µg/mL. 2. The combined herbal extract significantly suppressed the production of pro-inflammatory cytokines TNF-α (p<0.01) and IL-6 (p<0.001) in LPS-induced RAW264.7 macrophages in a concentration-dependent manner.