Alzheimer’s disease (AD) is a neurodegenerative disorder responsible for 70–80 % of dementia cases. Aluminum, a neurotoxicant, accelerates AD progression through oxidative stress and neuroinflammation. Many phytochemicals have shown promise as alternative AD therapies. This study investigated the therapeutic effects of Persea americana (PA) and Tabebuia rosea (TR) ethanolic leaf extracts in aluminum chloride (AlCl 3 )-induced AD in male rats. GC–MS analysis identified phytocompounds in the extracts. Forty-two male rats (70–100 g) were divided into six groups: control, AlCl 3 -only, TR-treated, PA-treated, combined extracts, and donepezil-treated (standard AD drug) groups. Biochemical and histopathological analyses were conducted on brain tissues. In silico analysis docked Beta-secretase (BACE1) against Elenbecestat and extract phytochemicals. AlCl 3 exposure significantly increased acetylcholinesterase (AChE) activity and malondialdehyde (MDA) levels while reducing glutathione (GSH) levels, with notable brain histopathology. PA and TR treatment reversed these effects, lowering AChE and MDA levels while increasing GSH. In silico analysis revealed that ethyl (9E,12E)-octadeca-9,12-dienoate and 9-octadecenoic acid, ethyl ester, exhibited superior docking scores and binding energies compared to Elenbecestat. These findings suggest PA and TR extracts as potential alternative treatments for AD.