Hypertension is the central pathophysiologic contributor to cardiovascular morbidity and mortality. Senecio serratuloides is used for the folkloric treatment of hypertension, diarrhoea, skin disorder and other health problems. Serial extraction using hexane,dichloromethane,ethyl acetate and methanol yielded 4 fractions of S. serratuloides (SSHex, SSDCM, SSEA and SSMOH respectively). The fractions were tested for their phytochemical constituents,acute toxicity, antioxidant capacity [Ferric Reducing Antioxidant Power (FRAP), 2,2’- azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) assays] and antihypertensive properties in L-NAME induced hypertension. Fraction SSEA and SSMOH had all 8 phytochemicals tested whileSSHex had 5 and SSDCM had 3.FractionSSMOHhad the highest flavonoid (34.8±0.4 µgQE/mg extract) and phenol (185.9±0.5µgGAE/mg extract) contents. The LD50 of SSEA and SSMOH were 3807.9 and 2154.1 mg/ml respectively while that of SSHex and SSDCM were greater than 5000 mg/ml. SSEA and SSMOH had better antioxidant capacity (IC50 1.09 and 0.41 mg/ml respectively) compared to SSDCM and SSHex (IC50 2.38 and 11.79 mg/ml respectively). Simultaneous co-administration of SSEA or SSMOH and L-NAME significantlyinhibited increases in SBP(11±1 and 13±0.1 mmHg)and DBP (5± and -7±4 mmHg) respectively compared to L-NAME control (SBP:23±2 mmHg and DBP: 30±3 mmHg).From theSSEA and SSMOH extracts, 2 sub-fractions were isolated by column chromatography and found to be potent antihypertensive agents. Results from this study suggests that S. serratuloides may be a great source of antioxidants and a potential antihypertensive agent.