The Cactus have been used in traditional medicine for years by the ancient people to cure several diseases such as Diabetes mellitus, The aim of this study is to carry out investigation on the neuroprotective effects of cactus extract on hippocampus of streptozotocin induced diabetic Wistar rats by assessing the histoarchitecture and histochemical indices. Thirty male adult Wistar rats were randomly choosed into five groups made up of six Wistar rats each, control, Cactus only, diabetic+cactus, diabetic+ metformin, diabetic only groups. The induction of Diabetes was done using Streptozotocin at a dose of 70 mg/kg bw intraperitoneally, after 72 hours of established hyperglyemia the treatment commences with aqueous extract of cactus at 100mg/kg bw and Metformin at 100 mg/kg bw respectively and was given orally for 4 weeks by using oral gastric cannula. The results showed significant decrease in average body weight and relative brain weight in diabetic group compared to diabetic+cactus and diabetic+metformin group(p<0.05). Diabetic group had significantly different blood glucose level from normal control, diabetic+cactus and diabetic+metformin (p<0.05). The histological findings showed that majority of the cells in diabetic group were necrotic while Diabetic + cactus and Diabetic + Metformin are similar to control. The analysis of the Glucose-6-phosphate dehydrogenase (G-6-PDH), lactate dehydrogenase (LDH) and reduced glutathione (GSH) activities in the Hippocampus revealed that the rats in the diabetic+cactus and diabetic+metformin are similar to the control group. The aqueous extract of cactus could be beneficial in averting the damage caused by Diabetes mellitus.