A phytopreparation based on the CO₂ extract of Arctium tomentosum Mill. root (AT) was evaluated for its safety and anti-inflammatory potential in Swiss albino mice. Acute and 28-day subacute oral toxicity studies demonstrated that AT, at doses up to 5000 mg/kg (acute) and 400 mg/kg (subacute), did not induce mortality, clinical signs of toxicity, or adverse effects on body weight, relative organ weights, or hematological and biochemical parameters. Histopathological analyses confirmed preserved tissue architecture in major organs, indicating the absence of structural toxicity. Anti-inflammatory activity was assessed using xylene-induced ear edema and LPS-induced systemic inflammation models. AT significantly reduced ear edema and suppressed the production of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in a dose-dependent manner. Additionally, AT exhibited potent hepatoprotective and nephroprotective effects, as reflected by the stabilization of ALT, AST, SCr, and BUN levels. Histological examination of inflamed tissues corroborated these findings. Overall, AT is well tolerated and demonstrates potent systemic anti-inflammatory and multi-organ protective properties, supporting its potential as a promising therapeutic candidate for inflammatory and oxidative stress-related conditions.