| Summary: | Seeds of most Arecaceae species are an underutilized raw material that can constitute a source of nutritionally relevant compounds. In this work, seeds of 24 Arecaceae taxa were analyzed for fatty acids (FAs) by GC-FID, for phenolics by HPLC-DAD and LC-MS, and for their antitumor activity against the HT-29 colorectal cancer cell line by the MTT assay. Lauric, oleic, and linoleic acids were the prominent FAs. Cocoseae species contained total FAs at 28.0–68.3 g/100 g seeds, and in other species total FAs were from 1.2 (<i>Livistona saribus</i>) to 9.9 g/100 g (<i>Washingtonia robusta</i>). <i>Sabal domingensis</i>, <i>Chamaerops humilis</i>, and <i>Phoenix dactylifera</i> var. <i>Medjool</i> had unsaturated/saturated FA ratios of 1.65, 1.33–1.78, and 1.31, respectively, and contained 7.4, 5.5–6.3, and 6.4 g FAs/100 g seeds, respectively. Thus, they could be used as raw materials for healthy oilseed production. Phenolics ranged between 39 (<i>Livistona fulva</i>) and 246 mg/100 g (<i>Sabal palmetto</i>), and of these, caffeic acid, catechin, dactylifric acid, and rutin had the highest values. (-)-Epicatechin was identified in most seed extracts by LC-MS. Hydroalcoholic extracts from five species showed a dose-dependent inhibitory effect on HT-20 cells growth at 72 h (GI<sub>50</sub> at 1533–1968 µg/mL). Overall, Arecaceae seeds could be considered as a cheap source of health-promoting compounds.
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