Oxidative stress and inflammation arising from hyperglycaemia have been identified as important targets in mitigating hyperglycaemia-induced organ dysfunction in diabetics. Chrysophyllum albidum fruit is commonly consumed as fruit snacks because of its beneficial effects in diabetes management. This study aim to evaluate the protective mechanisms of Chrysophyllum albidum fruit extract (CAFE) in streptozotocin-induced rats involving attenuation of oxidative stress, nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-gamma (PPAR-γ). CAFE was investigated for in vitro antioxidant and alpha amylase inhibitory activity. Male Wistar rats were made diabetic by single intraperitoneal injection of streptozotocin (60 mg/kg). The rats were then treated with CAFE (100 and 200 mg/kg) and pioglitazone (10 mg/kg) for two weeks. Fasting blood sugar (FBS), blood pressure parameters, lipid profile, oxidative stress parameters, NF-κB and PPAR-γ were determined. The extract showed antioxidant and alpha amylase inhibitory activities. CAFE significantly reduced STZ-induced hyperglycaemia after 7 and 14 days of treatment. CAFE also reduced STZ-induced elevation of diastolic blood pressure and mean arterial pressure and as well reduced atherogenic index in diabetic rats. It significantly decreased lipid peroxidation but increased the enzymatic and non-enzymatic antioxidant markers in the plasma, liver, kidney and pancreas. The immunohistochemical analysis revealed that CAFE significantly decreased hepatic and renal tissues NF-κB while increasing PPAR-γ gene expressions. The results of this study collectively showed the protective effect of Chrysophyllum albidum fruit extract in streptozotocin-induced diabetic rats via modulation of oxidative stress and NF-κB/ PPAR-γ expressions.