Aims: This study was designed to investigate the active chemical constituents and antioxidant capacities of saffron stigmas and turmeric rhizomes ethanolic extracts (ESE and ETE) respectively. D- galactose deleterious brain effects as well as the role of ESE and ETE supplementation against D-galactose intoxication were evaluated on male rat’s brain. Place of study: Biochemistry and Nutrition Department, Faculty of Women for Arts, Science and Education, Ain Shams University. Methodology: Fifty adult male Sprague-Dawley rats were divided into 5 groups; 10 rats each. Group (1): Healthy control; group (2): D-galactose control; rats were intoxicated with D-galactose (250mg/kg body weight /day/subcutaneously); group (3-5): D-galactose intoxicated rats and supplemented with (30mg /kg body weight /daily orally) of ESE, ETE and (15mg /kg body weight /daily orally) from each extract respectively for six weeks. Results: Research results revealed that saffron and turmeric ethanolic extracts contain active chemical constituents including polyphenols and flavonoids that possess high antioxidant activity. Biochemical analysis of brain tissues documented that injection with D-galactose caused significant increase (p≤0.05) in oxidative stress parameters including [advanced glycation end products (AGEs), protein carbonyl group (PCG), malondialdehyde (MDA) and nitric oxide (NO) Levels], pro-inflammatory markers like [tumor necrosis factor alpha (TNF-α) and interleukin -6 (IL-6) levels] , epigenetic marker [p16INK4a content] as well as neural cell markers [metallothoenins (MTs) and serotonin (5-HT) levels].On the other hand D-galactose intoxication caused significant decrease (p≤0.05) in brain antioxidants as [total antioxidant capacity (TAC), reduced glutathione (GSH) level and catalase (CAT) activity] as well as brain acetylcholinesterase (AChE) activity. All these results were proved by the microscopic examination and apoptotic markers immunohistochemical analysis of brain tissues that revealed degenerative changes in cerebral cortex and hippocampus. Oral administration of saffron and turmeric ethanolic extracts alone or in combination decreased brain oxidants, pro-inflammatory markers, epigenetic marker and neural cell markers levels while increased the levels and activities of antioxidants as well as AChE activity associated with an improvement of brain microscopic examination and immunohistochemical analysis. The most significant improvements (p≤0.05) were recorded in the group that supplemented with both extracts. Conclusion: Study results proved that saffron and turmeric ethanolic extracts active components were able to correct deleterious brain effects induced by D-galactose and using their mixture was more efficient in ameliorating brain toxicity than using each extract alone evidenced by biochemical analysis, microscopic examination as well as immunohistochemical determination of apoptotic markers in bmrain tissues. It is advised to add saffron and turmeric to human foods and to prepare their ethanolic extracts to be available for human beings due to their ability to preserve brain functions and structure as well as their potential to inhibit and retard brain aging and neuro-degeneration.