AbstractProdigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl₃)‐mediated AD‐like neurological alterations in rats. For this purpose, rats were gavaged either AlCl₃ (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl₃ induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre‐treatment significantly decreased acetylcholinesterase activity and restored the levels of brain‐derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na⁺/K⁺‐ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO‐1). Moreover, PDG exerted notable anti‐inflammatory effects via the lessening of interleukin‐1 beta, tumor necrosis factor‐alpha, cyclooxygenase‐2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro‐apoptotic (Bax and caspase‐3) levels and increases in anti‐apoptotic (Bcl‐2) biomarkers suggested an anti‐apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti‐inflammatory, and anti‐apoptotic activities of PDG establish it as a potent therapeutic option for AD.