Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). In these diseases, abnormally activated glial cells may cause non-autonomous neurotoxicity, which leads to stimulation of neurodegeneration. Thus, suppression of neuroinflammation is a potential strategy for treatment of neurodegenerative diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) are of interest in this context because epidemiological studies have shown that these drugs reduce the progression of neurodegenerative disease. In this review, we focus on evaluation of these effects in animal models. Several studies have shown that long-term treatment with ibuprofen improves cognitive dysfunction and histopathologic outcome in mouse models of AD. In contrast, NSAIDs have been shown to worsen dementia in rat models of neurological diseases, including models of brain injury and ischemia. We have found that ibuprofen significantly reduces protein aggregation and astrogliosis in dementia with Lewy bodies (DLB)-linked P123H β-synuclein transgenic mice, but produces little improvement of learning disability in behavior tests in these mice. Taken together, these results show that ibuprofen ameliorates neuroinflammation in neurodegenerative and neurological diseases, but may not improve cognitive function. Further studies are needed to understand the mechanisms underlying this critical issue. © 2013 by Nova Science Publishers, Inc. All rights reserved.