In the present study, we aimed to search and compare the biological activities of the ethanol (EtOH), methanol (MeOH), and ethylacetate (EtOAc) solvent extracts of the flower, stem, and root parts of two Helichrysum plants (H. chionophilum (Hc) and H. plicatum subsp. plicatum (Hp)). The antioxidant properties were determined by using (2,2-diphenyl-1-picrylhydrazyl) (DPPH) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The enzyme inhibitory effects of the extracts were investigated on butyrylcholinesterase (BChE), acetylcholinesterase (AChE), α-glucosidase, and α-amylase. Palmitic acid (C 16:0) was also determined as major fatty acids in the tested oils (31.21%–67.68%). In both plants, it was found that the EtOAc extracts of the flowers had a strong antioxidant and enzyme inhibitory effect. In conclusion, the results obtained in the present study showed that H. chionophilum and H. plicatum can be seen as a promising source for the natural bioactive compounds that can be used in therapeutic applications. Practical applications: The members of the genus Helichrysum have been widely taken for therapeutic purposes in traditional medicine as well as food. In this context, we investigated the chemical characterization and biological activities of two Helichrysum species extracts (H. chionophilum and H. plicatum subsp. plicatum). Antioxidant capacity, enzyme inhibition and anti-microbial effects were tested for biological activities. Chemical characterization was identified by high performance liquid chromatography (HPLC) (for phenolic) and gas chromatography-flame ioanization detector (GC-FID) (for fatty acids). Based on our findings, the species may be valuable for designing novel food products.