UNLABELLED: Alzheimer's disease (AD) is a significant health challenge in the 21st century. In spite of the approval of many new disease-modifying therapies for AD, the clinical advantages of these new treatments are less certain. AIM: This investigation was intended to determine the potential neuroprotective impact of morin hydrate (MH), zeolite clinoptilolite (ZC), and/or physical and mental activities (PhM) on an aluminum chloride (AlCl METHODS: Male Sprague Dawley rats were randomly allocated into seven groups. Group I was the control group. Groups II-VII were treated with AlCl RESULTS: PhM, MH, and ZC combined therapy exhibited a significant neuroprotective effect demonstrated by corrected catecholamines and tau and β-amyloid levels, as well as the antioxidant and anti-ferroptotic effects probably through Nrf2/HO-1/GPX4 and ACSL4 signaling pathways. In addition, combined therapy counteracted the inflammatory responses through modulating the TLR4/NF-κβ/NLRP3 inflammasome expression. Moreover, combined therapy groups showed the maximum improvement of both APOE4/LRP1 and Wnt3/β-catenin/GSK-3β signaling expressions. CONCLUSION: This research highlights the neuroprotective impact of MH and ZC plus PhM against AlCl