Elevated serum levels of uric acid are associated with an increased risk of hyperuricemia and gout. Recent attention has focused on the bioactive properties of plant extracts in preventing disease. Therefore, this study investigated the effects of 16 different extracts from four local plants on the inhibition of xanthine oxidase and the dissolution of uric acid, as well as the quantification of certain phytoconstituents and their haemolytic effects on human red blood cells. Results from quantitative phytochemical analysis revealed significant (p<0.0001) intra- and inter-specific variability in total phenols, flavonoids, tannins, uric acid, sodium, potassium, and calcium depending on the studied species and the type of solvent used in extraction. A total of 19 phenolic compounds were characterized and quantified using an ultrahigh-performance liquid chromatograph (UHPLC) coupled with an electrospray ionization (ESI) source operating in both negative and positive ionization modes mass spectrometry (LC-ESI-MS/MS), including phenolic acids, flavonoids and other polyphenols. The in vitro anti-gout activity results indicated that all extracts had the ability to express the inhibitory activity of xanthine oxidase and to dissolve uric acid at different levels. Therefore, the acetonic extracts of Cistus creticus and Plantago ciliata had the most significant xanthine oxidase inhibiting effect with values of 13.480±0.596 and 13.020±0.627 µg of Allopurinol/mg of dry residue, respectively. Moreover, their aqueous extracts showed the highest dissolving properties of uric acid (solubilities > 450 mg uric acid/L). These extracts also showed no toxic effect against isolated human erythrocytes and may be able to help improve the efficacy of new therapies for gouty arthritis.