Alzheimer’s disease (AD) is a multidimensional neurodegenerative disorder marked by progressive decline in cognition, influenced by various pathogenic pathways like amyloid-β accumulation, tau hyperphosphorylation, prolonged microglial activation, and oxidative stress. Although existing pharmacotherapies offer limited symptomatic relief, recent research highlights the neuroprotective potential of dietary carotenoids like lutein. Lutein is a naturally occurring xanthophyll recognized for its antioxidant and anti-inflammatory abilities, capable of crossing the blood-brain barrier and particularly accumulating in AD-sensitive brain regions, including the hippocampal region and occipital cortex. Recent studies indicate that lutein may inhibit microglial activation by downregulating key inflammatory mediators such as TNF-α, IL-1β, and IL-6, as well as obstructing pro-inflammatory pathways like NF-κB and MAPKs. This modulation shifts the microglial type from a damaging M1 state to a neuroprotective M2-like stage. Lutein, simultaneously, activates the Nrf2/HO-1 pathway and neutralizes reactive oxygen species (ROS), thus reducing oxidative stress, a recognized driver of amyloid pathology and neuronal degeneration in AD. Preclinical models have shown that lutein supplementation enhances cognitive performance, lowers amyloid accumulation, and preserves synaptic integrity. Despite the limited availability of human clinical data, observational studies correlate elevated lutein levels with improved cognitive outcomes in aging populations. Innovative delivery technologies, such as nano-formulations, may augment lutein’s cerebral bioavailability, hence enhancing its therapeutic efficacy. This chapter thoroughly examines lutein’s molecular pathways in reducing microglial activation and oxidative damage, highlighting its potential as a safe, multi-targeted approach in the management of AD.