Lead (Pb) toxicity is a great community health problem. Brain is the primary target organ of Pb intoxication. Ascorbic acid (AA) and Gallic acid (GA) have proven to show potential anti‑inflammatory and antioxidant properties during heavy metal intoxication. So, the current paper aimed to explore the possible protection of AA, GA, and their combination in the current model of Pb neurotoxicity. Fifty-six Wistar male albino rats were assigned into seven groups: control, AA alone (10 mg/kg, oral), GA alone (20 mg/kg, oral), Pb alone (40 mg/kg, intraperitoneal), AA/Pb, GA/Pb, and AA/GA/Pb combination groups. After one month of oral treatment, the animals were humanely killed, and brain cortical samples were extracted for biochemical measurement of the inflammatory and oxidative markers in the brain tissue homogenates. Moreover, the samples were subjected to structural and ultrastructural examinations using light and electron microscopic (EM) studies. Pb resulted in brain injury indicated by remarkable structural and ultrastructural changes evident by neuronal degeneration and reduction of healthy nerve cells. EM showed atrophic nerve cells with irregular outlines, swollen, rarefied mitochondria, and enlarged, fused electron-dense lysosomes indicating possible autophagic vacuoles. Also, a significant increase in the pro-inflammatory markers was noticed, as evident by the raised immunohistochemical expression of glial fibrillary acidic protein (GFAP), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α). In addition, the anti-inflammatory marker decreased, as denoted by the decline in superoxide dismutase (SOD) and catalase. All these alterations were lessened by AA and GA with great restoration in the AA/GA combination group, which showed almost normal histological, ultrastructural, and biochemical parameters. AA and GA are suggested to alleviate Pb‑induced neurotoxicity owing to the modulation of oxidative stress, inflammation, and apoptosis. However, the AA/GA combination shows the greatest effect as evidenced by biochemical, structural, and ultrastructural analyses.