Zygophyllum is one of the most important genus of the plant family Zygophyllaceae that grows in the desert and dry regions, is well-known for its anti-inflammatory, antioxidant, antibacterial and anticancer properties. three predominant species of genus Zygophyllum which grows in southern Algeria (Z. album, Z.cornutum and Z.gaetulum) (ZAl, ZCo and ZGa) were were analyzed for phenolic components by UPLC/MS-MS. Nineteen phenolic compounds were identified, including Esculin Hydrate, Catechin and Thymol as major constituents. The cytotoxicity assay of three Zygophyllum ethanolic extracts on Saccharomyces cerevisiae showed that ZAl and ZCo extracts are non-toxic at all tested concentrations. In contrast, the ZGa extract significantly decreased cell viability by about 50% at the highest concentration (10,000 μg/ml). The anti-inflammatory activity of Zygophyllum extracts varied significantly across different concentrations. Aspirin, used as a reference, showed a dose-dependent effect with a maximum inhibition of 72.7% at 20 mg/ml. At the same concentration, ZGa exhibited the strongest effect at 50.77%, followed by ZCo at 27.22% and ZAl at 17.70%. The IC50 values from the Alpha-amylase assay indicated significant differences in the potency of the tested samples. ZAl showed the highest potency with an IC50 of 3.7, indicating effectiveness but requiring more concentration than Acarbose.