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Diabetes Mellitus is a metabolic disorder characterized by high blood glucose levels, causing significant morbidity and mortality rates. This study investigated the antidiabetic, neuroprotective, and antioxidant effects of ethanol extracts of Parkia biglobosa (PB) leaves and seeds in streptozotocin (STZ)-induced diabetic rats. The administration of STZ significantly elevated fasting blood glucose levels (FBGL) to 355-400 mg/mL compared to 111 mg/mL in normal controls, indicating hyperglycemia. Treatment with PB extracts at 100 mg/kg and 200 mg/kg significantly (p < 0.05) reduced FBGL in a dose-dependent manner. No significant difference was observed between the effects of metformin and PB extracts at 200 mg/kg. Cognitive dysfunction, assessed using the Y-maze test, was significantly improved in groups treated with PB extracts (p < 0.05), particularly at 200 mg/kg, through inhibition of cholinesterase activity and protection against oxidative damage. Both PB extracts also demonstrated significant inhibition (p < 0.05) of α-amylase and α-glucosidase activity, reducing postprandial hyperglycemia, with a stronger inhibition at 200 mg/kg. Additionally, PB extracts significantly increased catalase (CAT) and superoxide dismutase (SOD) activities, reversing the diabetes-induced decline in antioxidant enzyme levels. Monoamine oxidase (MAO) activity, elevated in diabetic conditions, was significantly downregulated by PB treatment, further contributing to neuroprotection. The neuroprotective effects may be attributed to the inhibition of cholinesterase and MAO, which help maintain neurotransmitter levels, alongside the antioxidant properties that mitigate oxidative stress in the brain. These findings suggest that PB extracts could serve as a natural therapeutic agent for diabetes management, with its effects comparable to metformin at higher doses., Competing Interests: Declarations. Consent for publication: All authors have read and given approval for the publication of the manuscript. Consent to participate: Not applicable. Ethical approval: An approval (BUHREC 1023/23) for animal experimentation and methodologies was obtained from the Babcock University Health Research Ethics Committee (BUHREC), Ogun State, Nigeria. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)