Pergularia tomentosa (P. tomentosa) is widely used as anti-rheumatic, laxative, abortive, and as a treatment for some skin disease in the traditional medicine. Our study aims to investigate the antioxidant properties of different extracts of P. tomentosa, study the major phenolic and flavonoids components of these extracts. Three P. tomentosa samples were collected from Sohag, Egypt. These samples were extracted in methanol (PTi, PTii and PTiii) and ethanol (PTiv). Total phenolic content (TPC), total flavonoid content (TFC) and the DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant activity of P. tomentosa extracts were investigated using colorimetric assays. PTi has the highest TPC (32.46±1.29 mg GAE/g DW), followed by PTiii sample (24.56 ± 1.97 mg GAE/g DW). On the other hand, PTiii revealed the highest TFC (11.48 ± 0.16 QE/g DW) and showed the potent antioxidant activity against DPPH with the IC₅₀= 0.340 mg/mL, while the IC₅₀ of PTiv was 0.640 mg/mL. High performance liquid chromatography (HPLC) analysis of PTiii extract exhibited the presence of Gallic acid (16.4%), Ferulic acid (11.5%), Chlorogenic acid (9%), Vanillin (7%), Naringenin (3.4), Syringic acid (2.9%), Caffeic acid (2.1%), Hesperetin (1.6%), and Coumaric acid (1.55%), however, PTiv showed different concentrations of these components, such as Gallic acid (28.7%), Ferulic acid (14.14%), Caffeic acid (11.66%), Syringic acid (10.5%), Naringenin (9.9%), Catechin (6.5%), Chlorogenic acid (5.0%), Hesperetin (3.6%), Coumaric acid (2.6%), Kaempferol (2.6%), Cinnamic acid (1.5%), and Vanillin (1.3%). These results indicated that the P. tomentosa may be used in therapeutic applications with a potential to reduce the oxidative stress.