The content of bioactive compounds in four brown and one red algae from the Adriatic Sea ( , , and ) is explored. The efficiency of two different extraction methods viz. ultrasound-assisted extraction (UAE) and matrix solid-phase dispersion (MSPD) to obtain the extracts rich in phenolic compounds was compared. The effect of the extraction solvent to modulate the phenolic profile was assessed. In general, the mixture ethanol/water in an isovolumetric proportion showed the best results. The total phenolic content (TPC) and antioxidant activity (AA), as well as the individual polyphenolic profile, were evaluated for five target algae. TPC values ranged between 0.2 mg GAE/g (for ) and 38 mg GAE/g (for ). Regarding the quantification of individual polyphenols by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, the presence of a high number of hydroxybenzoic acid derivatives (mainly of 3- and 4-hydroxybenzoic acids) in all species was noted. In their concentrations reached up to 500 mg/kg. IC values (ABTS assay) ranged between 44 mg/L (for ) and 11,040 mg/L (for ). This work contributes to the in-depth characterization of these little-explored algae, showing their potential as a natural source of phenolic compounds.