Neuroinflammation is increasingly recognized as a pivotal factor in the pathogenesis of various neurological disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and stroke. This chapter critically examines the potential of natural anti-inflammatory compounds as therapeutic agents for modulating neuroinflammatory processes and mitigating neurodegenerative progression. Focusing on bioactive phytochemicals such as curcumin, resveratrol, omega-3 fatty acids, and green tea polyphenols, the discussion encompasses their mechanisms of action, which include the inhibition of pro-inflammatory cytokine production, suppression of key signaling pathways (e.g., NF-κB, MAPK), and enhancement of antioxidant defenses. Preclinical evidence from in vitro studies and animal models is reviewed to highlight the neuroprotective effects of these compounds, demonstrating their capacity to reduce microglial activation, attenuate oxidative stress, and improve functional outcomes. The chapter also addresses the translational challenges associated with the clinical application of natural compounds, notably issues of bioavailability, blood-brain barrier permeability, and extract standardization. Emerging strategies such as advanced drug delivery systems, combination therapies, and personalized medicine approaches are discussed as promising avenues to overcome these limitations. Collectively, the insights presented underscore the potential of natural anti-inflammatory compounds as complementary agents in the therapeutic arsenal against neurodegenerative diseases, warranting further investigation through rigorous clinical trials and interdisciplinary research efforts.