Neurodegenerative diseases are marked by progressive neuronal dysfunction and currently lack effective therapeutic interventions. Microglia, as the primary immune cells of the central nervous system, play a central role in neuroinflammation, thereby accelerating neurodegeneration. This study investigated the neuroprotective potential of putrescine by examining its effects on cell viability and inflammatory gene expression in BV2 microglial cells. BV2 cells were treated with putrescine alone or in combination with lipopolysaccharide (LPS) to mimic inflammatory conditions. Cell viability was evaluated using the MTT assay, while the expression levels of PADI2, CRP, MEK1, ERK2, and IL-6 were analyzed by qPCR using GAPDH as a reference gene. Putrescine treatment significantly downregulated PADI2, CRP, MEK1, and ERK2 expression, whereas IL-6 expression was markedly increased. In parallel, molecular docking analysis demonstrated that putrescine binds selectively and stably to the B-chain of the IL6/IL6R/IL6ST complex through multiple hydrogen bonds involving residues such as ASP134, VAL85, ALA130, and THR137. Despite its low molecular weight, putrescine exhibited a favorable binding profile. Collectively, these findings suggest that putrescine modulates microglial inflammatory responses and may hold therapeutic potential for neurodegenerative diseases.