ABSTRACT Background Botulinum toxin type A (BoNT‐A) formulations are extensively employed in aesthetic and therapeutic dermatology. However, their immunomodulatory and pro‐inflammatory properties remain incompletely characterized, particularly concerning dermal fibroblasts. Aims This study aimed to evaluate and compare the effects of three commercially available BoNT‐A formulations—Bocouture, Vistabex, and Azzalure—on the expression of interleukin‐6 (IL‐6), a key pro‐inflammatory cytokine, in cultured adult human dermal fibroblasts. Patients/Methods Human dermal fibroblasts were cultured in vitro and treated with increasing concentrations of Bocouture, Vistabex, and Azzalure. IL‐6 expression was measured at 24, 48, and 72 h posttreatment using an enzyme‐linked immunosorbent assay (ELISA). Cell viability was assessed by MTT assay to exclude cytotoxic effects. Each condition was tested in triplicate. Data were analyzed using one‐way ANOVA with Bonferroni's multiple comparisons posttest. Results Vistabex significantly increased IL‐6 expression at multiple time points, with the most marked elevation observed at 0.5 U/mL after 24 h ( p ≤ 0.0001). Conversely, Bocouture and Azzalure did not induce significant changes in IL‐6 levels across all tested concentrations and time intervals. No formulation reduced fibroblast viability below 80%, confirming the absence of relevant cytotoxicity. Conclusions These findings suggest a formulation‐specific inflammatory response to BoNT‐A in dermal fibroblasts, with Vistabex eliciting a notable upregulation of IL‐6. The observed differences may be attributed to distinct structural or excipient‐related properties and warrant further investigation to clarify their clinical implications, especially in patients with a predisposition to inflammatory skin responses.