Helichrysum gymnocephalum essential oil (EO) was prepared by hydrodistillation of its leaves and characterized by GC-MS and quantified by GC-FID. Twenty three compounds were identified. 1,8-Cineole (47.4%), bicyclosesquiphellandrene (5.6%), γ-curcumene (5.6%), α-amorphene (5.1%) and bicyclogermacrene (5%) were the main components. Our results confirmed the important chemical variability of H. gymnocephalum. The essential oil was tested in vitro for cytotoxic (on human breast cancer cells MCF-7), antimalarial (Plasmodium falciparum: FcB1-Columbia strain, chloroquine-resistant) and antioxidant (ABTS and DPPH assays) activities. H. gymnocephalum EO was found to be active against MCF-7 cells, with an IC(50) of 16 ± 2 mg/L. The essential oil was active against P. falciparum (IC(50) = 25 ± 1 mg/L). However, the essential oil exhibited a poor antioxidant activity in the DPPH (IC(50) value > 1,000 mg/L) and ABTS (IC(50) value = 1,487.67 ± 47.70 mg/L) assays. We have reviewed the existing results on the anticancer activity of essential oils on MCF-7 cell line and on their antiplasmodial activity against the P. falciparum. The aim was to establish correlations between the identified compounds and their biological activities (antiplasmodial and anticancer). β-Selinene (R² = 0.76), α-terpinolene (R² = 0.88) and aromadendrene (R² = 0.90) presented a higher relationship with the anti-cancer activity. However, only calamenene (R² = 0.70) showed a significant correlation for the antiplasmodial activity.