Herbal medicinal products are gaining attention due to their accessibility and relative safety, yet challenges such as inconsistent efficacy and potential cytotoxicity remain. In this study, to overcome these limitations, we applied a plasma-based ionization method to a combination of Perilla frutescens and Taraxacum platycarpum Dahlst and evaluated its biological effects. THP-1 and Raw 264.7 cells were treated with either ionized or non-ionized extracts, followed by assessments of cell morphology, confluency, viability, and pro-inflammatory cytokine production. Ionization effectively reduced cytotoxic effects, as evidenced by preserved normal cell morphology and viability, and the absence of elevated proinflammatory cytokines. Notably, non-ionized extracts alone induced significant levels of pro-inflammatory cytokines in both cell types, suggesting a potential risk of undesirable immune activation. Although anti-inflammatory activity was not significantly enhanced, it was maintained in Raw 264.7 cells. In THP-1 cells, the ionized extract showed a trend toward enhanced anti-inflammatory activity, with reduced variability compared to the non-ionized extract. These findings suggest that plasma-based ionization may stabilize and improve the reliability of herbal extract efficacy without introducing adverse effects.