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This work focuses on Cistus monspeliensis L. aerial parts (AP) and roots (R) extracts, investigating the anti-inflammatory and antioxidant potential of the two organs in comparison. At dosages between 1.56 and 6.25 µg/mL, both extracts showed a protective effect against LPS inflammatory stimulus on a macrophage cell line (RAW 264.7). Interestingly, only R was able to significantly reduce both IL-1β and IL-6 mRNA gene expression in the presence of LPS. Moreover, the treatment of a neuroblastoma cell line (SH-SY5Y) with AP and R at 6.25 µg/mL increased the cell survival rate by nearly 20% after H2O2 insult. However, only R promoted mitochondria survival, exhibited a significantly higher production of ATP and a higher activity of the enzyme catalase than the control. Both AP and R had similar primary metabolites; in particular, they both contained 1-O-methyl-epi-inositol. Labdane and methoxylated flavonoids were the most characteristic compounds of AP, while R contained mainly catechins, gallic acid, and pyrogallol derivatives. Considering the importance of elemental composition in plants, the inorganic profile of AP and R was also investigated and compared. No potentially toxic elements, such as Pb, were detected in any sample.