Medicinal plants are a source of a wide range of bioactive compounds, such as alkaloids, terpenes, steroids and phenolic compounds, which are responsible for multiple biological effects [1, 2]. In the present work, the phenolic composition and bioactive potential of the aqueous and hydroethanolic extracts of Equisetum giganteum L. and Tilia platyphyllos Scop. were evaluated. The phenolic compounds were determined using a Hewlett-Packard 1100 chromatograph, with a diode array detector coupled to a MS detector API 3200 Qtrap through an ESI source and a triple quadrupole-ion trap mass analyser, while the bioactive properties were evaluated in terms of antioxidant, anti-inflammatory, and cytotoxic activities. The hydroethanolic extracts revealed higher amounts of phenolic compounds than infusions, being the concentration of flavonoids (81% of the phenolic composition) remarkably higher than the phenolic acids content (19%), in both species and extracts. T. platyphyllos presented a higher phenolic content (50.4 ± 0.4 mg/g of hydroethanolic extract and 11.65 ± 0.05 mg/g of lyophilized infusion), than E. giganteum (21.7 ± 0.4 mg/g and 4.98 ± 0.03 mg/g, respectively). Moreover, kaempferol- O-glucoside-O-rutinoside was the most abundant flavonoid in E. giganteum extract, while protocatechuic acid and (−)-epicatechin were the most abundant phenolic acid and flavonoid, respectively, in T. platyphyllos extract. Regarding the bioactive assays, both extracts obtained from T. platyphyllos showed the highest potential and none of the extracts showed toxicity in non-tumor liver cells. These biological properties were highly correlated with its content and composition in phenolic compounds. Thus, it would be interesting to evaluate the in vivo efficacy of both plant extracts to unveil the involved modes of action and to establish effective therapeutic doses.