Endothelial vascular dysfunctions are prevalent among diabetic patients, significantly impacting their quality of life and prognosis. This study examined the effects of polyphenol-rich extracts from Ocimum gratissimum leaves on oxidative stress markers, serum lipid profiles, and angiotensin-converting enzyme activity in diabetic cardiac tissue. Forty Wistar rats (150–220 g) were divided into five groups: normal control, diabetic control, low-dose Ocimum gratissimum (122.46 mg/kg), medium-dose Ocimum gratissimum (244.98 mg/kg), and a positive control (standard diabetic drug). All rats except the normal control group were made diabetic via an intraperitoneal injection of 50 mg/kg streptozotocin, followed by 28 days of extract administration. Diabetes induction led to a significant (p<0.05) disruptions in lipid profiles, oxidative stress markers, and ACE activity. Treatment with Ocimum gratissimum extracts at both doses significantly (p<0.05) decreased triglyceride, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol. Lipid peroxidation marker, malondialdehyde, was significantly (p<0.05) decreased, and antioxidant enzyme activities significantly (p<0.005) improved. ACE activity was significantly (p<0.05) reduced, approaching control levels. These results suggest that the polyphenol-rich extract of Ocimum gratissimum exerts antioxidant and cardio-protective effects, improving vascular functions in diabetic rats by improving lipid profiles, reducing oxidative stress, and suppressing ACE activity.