Background: Lead is a heavy metal that is widespread in nature and has extremely strong chemical toxicity in the human body especially harmful to the human nervous system. Lactic acid bacteria (LAB) can be used to maintain the balance of the intestinal microbiota, and recent reports have shown that LAB can remove metal ions through adsorption. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral LF-SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity.Results: Through electron microscopy and energy spectrum analysis, it was found that the surface of the lactic acid bacteria adsorbed a large amount of lead ions, and the O and N elements in the bacteria were significantly reduced. Animal experiments showed that LF-SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue, reduced the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and blood urea nitrogen (BUN) in rat serum, and increased δ-aminolevulinic acid dehydratase (δ-ALAD) activity in serum. Further, LF-SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats. LF-SCHY34 inhibited the secretion of glutamate and the activity of monoamine oxidase in brain tissue, promoted the synthesis of glutamine (Glu), norepinephrine (NE), and cyclic adenosine monophosphate (cAMP), and increased the activities of glutamine synthetase (GS), acetylcholinesterase (AchE), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity in rat brain tissues such as calmodulin (CaM), protein kinase A (PKA), brain-derived neurotrophic factor (BDNF), c-fos, c-jun was increased by LF-SCHY as was the expression of the antioxidation genes and the anti-apoptotic gene. Conclusions: Compared with the lead poisoning treatment drug EDTA, LF-SCHY34 not only had greater lead discharge capacity than EDTA, but also had a greater alleviating effect on organ damage and oxidative damage caused by lead. As a food-grade LAB, LF-SCHY34 has great potential and research value for removing heavy metals from food and alleviating the toxicity of heavy metals.