Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects more than five million Americans and is characterized by a progressive loss of memory, loss of cholinergic neurons in the basal forebrain, formation of amyloid plaques and neurofibrillary tangles, and an increase in oxidative stress. Recent studies indicate that dietary supplements of antioxidants and omega-3 and omega-6 fatty acids may reduce the cognitive deficits in AD patients. The current study tested a combinatorial treatment of antioxidants from tart cherry extract and essential fatty acids from Nordic fish and emu oils for reducing cognitive deficits in the mu-p75 saporin (SAP)-induced mouse model of AD. Mice were given daily gavage treatments of Cerise(®) Total-Body-Rhythm™ (TBR; containing tart cherry extract, Nordic fish oil, and refined emu oil) or vehicle (methylcellulose) for 2 weeks before intracerebroventricular injections of the cholinergic toxin, mu-p75 SAP, or phosphate-buffered saline. The TBR treatments continued for an additional 17 days, when the mice were tested on a battery of cognitive and motor tasks. Results indicate that TBR decreased the SAP-induced cognitive deficits assessed by the object-recognition, place-recognition, and Morris-water-maze tasks. Histological examination of the brain tissue indicated that TBR protected against SAP-induced inflammatory response and loss of cholinergic neurons in the area around the medial septum. These findings indicate that TBR has the potential to serve as an adjunctive treatment which may help reduce the severity of cognitive deficits in disorders involving cholinergic deficits, such as AD.